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Easy access to evidence-based information on COVID-19 within an infodemic has been a challenging task. Chatbots have been introduced in times of emergency, when human resources are stretched thin and individuals need a user-centered resource. The World Health Organization Regional Office for Europe and UNICEF (United Nations Children's Fund) Europe and Central Asia came together to build a chatbot, HealthBuddy+, to assist country populations in the region to access accurate COVID-19 information in the local languages, adapted to the country context. Working in close collaboration with thematic technical experts, colleagues and counterparts at the country level allowed the project to be tailored to a diverse range of subtopics. To ensure that HealthBuddy+ was relevant and useful in countries across the region, the 2 regional offices worked closely with their counterparts in country offices, which were essential in partnering with national authorities, engaging communities, promoting the tool, and identifying the most relevant communication channels in which to embed HealthBuddy+. Over the past 2 years, the project has expanded from a web-based chatbot in 7 languages to a multistream, multifunction chatbot available in 16 regional languages, and HealthBuddy+ continues to expand and adjust to meet emerging health emergency needs.

Background Sodium glucose cotransporter‐2 inhibitors reduce systolic blood pressure (SBP), but whether they affect SBP variability is unknown. There also remains uncertainty regarding the prognostic value of SBP variability for different clinical outcomes. Methods and Results Using individual participant data from the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program and CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial, we assessed the effect of canagliflozin on SBP variability in people with type 2 diabetes across 4 study visits over 1.5 years as measured by standard deviation, coefficient of variation, and variability independent of the mean. We used multivariable Cox regression models to estimate associations of SBP variability with cardiovascular, kidney, and mortality outcomes. In 11 551 trial participants, canagliflozin modestly lowered the standard deviation of SBP variability (−0.25 mm Hg [95% CI, –0.44 to −0.06]), but there was no effect on coefficient of variation (0.02% [95% CI, –0.12 to 0.16]) or variability independent of the mean (0.08 U [95% CI, –0.11 to 0.26]) when adjusting for correlation with mean SBP. Each 1 standard deviation increase in standard deviation of SBP variability was independently associated with higher risk of hospitalization for heart failure (hazard ratio [HR], 1.19 [95% CI, 1.02–1.38]) and all‐cause mortality (HR, 1.12 [95% CI, 1.01–1.25]), with consistent results observed for coefficient of variation and variability independent of the mean. Increases in SBP variability were not associated with kidney outcomes. Conclusions In people with type 2 diabetes at high cardiovascular risk or with chronic kidney disease, higher visit‐to‐visit SBP variability is independently associated with risks of hospitalization for heart failure and all‐cause mortality. Canagliflozin has little to no effect on SBP variability, independent of its established SBP‐lowering effect. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01032629, NCT01989754, NCT02065791.

Abstract There is sparse evidence of how well haematological targets are met in practice for essential thrombocythemia (ET) and polycythaemia vera (PV) patients. Patient data was collected between 2008 and 2020 from two UK NHS Trusts for ET and PV patients. Longitudinal changes in peripheral blood counts, including the proportion of patients meeting peripheral blood count remission, was modelled. Relative risk of cardiovascular‐related events for patients achieving remission within 3‐months was estimated. A total of 620 ET and 429 PV patients were analysed. For high‐risk patients, haematological parameters decreased in the first months of observation then stabilised within normal reference ranges until year 5. Total time spent in peripheral blood count remission was 39.2% for ET and 29.1% for PV. A lower proportion of ET patients reached target platelet counts (48.3%) compared to WBC (79.1%), whilst PV patients were less likely to reach target haematocrit levels (56.9%) compared to platelets (77.3%) or WBC (74.6%). There was no statistically significant association between reaching target blood counts within 3‐months and cardiovascular risk. Complete haematological remission remains a challenging target in managing PV and ET, however this study was unable to show statistically‐significant evidence that this was associated with increased risk of cardiovascular events.

Urinary tract infections (UTIs) are a major cause of emergency hospital admissions, but it remains challenging to diagnose them reliably. Application of machine learning (ML) to routine patient data could support clinical decision-making. We developed a ML model predicting bacteriuria in the ED and evaluated its performance in key patient groups to determine scope for its future use to improve UTI diagnosis and thus guide antibiotic prescribing decisions in clinical practice. We used retrospective electronic health records from a large UK hospital (2011-2019). Non-pregnant adults who attended the ED and had a urine sample cultured were eligible for inclusion. The primary outcome was predominant bacterial growth ≥104 cfu/mL in urine. Predictors included demography, medical history, ED diagnoses, blood tests, and urine flow cytometry. Linear and tree-based models were trained via repeated cross-validation, re-calibrated, and validated on data from 2018/19. Changes in performance were investigated by age, sex, ethnicity, and suspected ED diagnosis, and compared to clinical judgement. Among 12,680 included samples, 4,677 (36.9%) showed bacterial growth. Relying primarily on flow cytometry parameters, our best model achieved an area under the ROC curve (AUC) of 0.813 (95% CI 0.792-0.834) in the test data, and achieved both higher sensitivity and specificity compared to proxies of clinician's judgement. Performance remained stable for white and non-white patients but was lower during a period of laboratory procedure change in 2015, in patients ≥65 years (AUC 0.783, 95% CI 0.752-0.815), and in men (AUC 0.758, 95% CI 0.717-0.798). Performance was also slightly reduced in patients with recorded suspicion of UTI (AUC 0.797, 95% CI 0.765-0.828). Our results suggest scope for use of ML to inform antibiotic prescribing decisions by improving diagnosis of suspected UTI in the ED, but performance varied with patient characteristics. Clinical utility of predictive models for UTI is therefore likely to differ for important patient subgroups including women

Abstract Recent studies have found that oxygen saturation (SpO2) variability analysis has potential for noninvasive assessment of the functional connectivity of cardiorespiratory control systems during hypoxia. Patients with sepsis have suboptimal tissue oxygenation and impaired organ system connectivity. Our objective with this report was to highlight the potential use for SpO2 variability analysis in predicting intensive care survival in patients with sepsis. MIMIC‐III clinical data of 164 adults meeting Sepsis‐3 criteria and with 30 min of SpO2 and respiratory rate data were analyzed. The complexity of SpO2 signals was measured through various entropy calculations such as sample entropy and multiscale entropy analysis. The sequential organ failure assessment (SOFA) score was calculated to assess the severity of sepsis and multiorgan failure. While the standard deviation of SpO2 signals was comparable in the non‐survivor and survivor groups, non‐survivors had significantly lower SpO2 entropy than those who survived their ICU stay (0.107 ± 0.084 vs. 0.070 ± 0.083, p

Underground salt caverns allow large hydrogen storage capacities at low specific costs. Such storage is required to balance fluctuating hydrogen supply and constant demand of large consumers as a methanol plant from the Carbon2Chem® project. The geological and technical feasibility for developing up to 168 Mio. m3 (n.c.) or 595 GWh of working gas capacity until 2040 at a location in the Lower Rhine Bay is described. Various options for realization as well as a novel process for cavern leaching parallel to hydrogen storage operation are evaluated. Further work is required including geological exploration and optimization of brine production. The main hurdles for investment decisions are the political uncertainties on the hydrogen storage market design and on the ramp‐up of the hydrogen market. [ABSTRACT FROM AUTHOR]

The fracture characteristics of severely plastically deformed (SPD) materials exhibit large variations in the quasi-static fracture resistance depending on factors such as the investigated material, testing temperature and grain aspect ratio. Especially the latter one is considered to control the frequently observed orientation dependent fracture toughness. A question that arises thereby is how the fracture properties for certain testing directions could be actively tuned by tailoring the grain aspect ratio. In this contribution this issue has been investigated by changing the aspect ratio of ultrafine-grained tantalum processed by high pressure torsion through post-rolling operations which induced a substantial increase of the grain length while keeping the strength on a comparable level. Samples in interesting testing directions were manufactured and tested. The increase of the aspect ratio results in the technically significant testing directions to an enhancement of the fracture toughness. Delamination toughening, which is promoted by the change of the aspect-ratio, has been indentified to be the main cause for the toughness enhancement and represents therefore a feasible pathway for optimizing the damage tolerance of SPD-processed materials.

Abstract Background Urinary tract infection (UTI) is a leading cause of hospital admissions and is diagnosed based on urinary symptoms and microbiological cultures. Due to lags in the availability of culture results of up to 72 h, and the limitations of routine diagnostics, many patients with suspected UTI are started on antibiotic treatment unnecessarily. Predictive models based on routinely collected clinical information may help clinicians to rule out a diagnosis of bacterial UTI in low-risk patients shortly after hospital admission, providing additional evidence to guide antibiotic treatment decisions. Methods Using electronic hospital records from Queen Elizabeth Hospital Birmingham (QEHB) collected between 2011 and 2017, we aim to develop a series of models that estimate the probability of bacterial UTI at presentation in the emergency department (ED) among individuals with suspected UTI syndromes. Predictions will be made during ED attendance and at different time points after hospital admission to assess whether predictive performance may be improved over time as more information becomes available about patient status. All models will be externally validated for expected future performance using QEHB data from 2018/2019. Discussion Risk prediction models using electronic health records offer a new approach to improve antibiotic prescribing decisions, integrating clinical and demographic data with test results to stratify patients according to their probability of bacterial infection. Used in conjunction with expert opinion, they may help clinicians to identify patients that benefit the most from early antibiotic cessation.

Abstract Background Suspected urinary tract infection (UTI) syndromes are a common reason for empirical antibiotics to be prescribed in the Emergency Department (ED), but differentiating UTI from other conditions with a similar presentation is challenging. We investigated how often an ED diagnosis of UTI is confirmed clinically/microbiologically, and described conditions which present as UTI syndromes. Methods Observational study using electronic health records from patients who attended the ED with suspected UTI and had a urine sample submitted for culture. We compared the ED diagnosis to diagnosis at discharge from hospital (ICD-10 codes), and estimated the proportion of cases with clinical/microbiological evidence of UTI. Results Two hundred eighty nine patients had an ED diagnosis of UTI syndrome comprising: lower UTI (191), pyelonephritis (56) and urosepsis (42). In patients admitted to hospital with an ED diagnosis of lower UTI, pyelonephritis or urosepsis, clinical/microbiological evidence of UTI was lacking in 61/103, 33/54 and 31/42 cases respectively. The ED diagnosis was concordant with the main reason for admission in less than 40% of patients with UTI syndromes, and antibiotics were stopped within 72 h in 37/161 patients. Conclusions Clinical/microbiological evidence of UTI was lacking in 60–70% of patients, suggesting scope to revise empirical prescribing decisions for UTI syndromes in light of microbial culture and clinical progression.

BackgroundGaza has been under land, sea, and aerial closure for 13 years, during which time Palestinian patients from Gaza have been required to obtain Israeli-issued permits to access health facilities in the West Bank (including east Jerusalem), as well as in Israel and Jordan. Specific groups, like cancer patients, have a high need for permits due to lack of services in Gaza. The approval rate for patient permits to exit Gaza dropped from 94% in 2012 to 54% in 2017. We aimed to assess the impact of access restrictions due to permit denials/delays on all-cause mortality for cancer patients from Gaza referred for chemotherapy and/or radiotherapy.MethodsThis study matched 17,072 permit applications for 3,816 cancer patients referred for chemotherapy and/or radiotherapy from 1 January 2008 to 31 December 2017 with referrals data for the same period and mortality data from 1 January 2008 to 30 June 2018. We carried out separate analyses by period of first application (2008-14; 2015-17), in light of varying access to Egypt during these times. Primary analysis compared survival of patients according to their first referral decision (approved versus denied/delayed) using Kaplan-Meier method and Cox regression.FindingsMortality in patients unsuccessful in permit applications from 2015-17 was significantly higher than mortality among successful patients, with a hazard ratio of 1·45 (95% CI: 1·19-1·78, pInterpretationLimitations to patient access due to unsuccessful applications for permits to exit the Gaza Strip had a significant impact on mortality for cancer patients applying for chemotherapy and/or radiotherapy in the period 2015-17. The substantially higher number of annual unsuccessful permit applications from 2015, combined with severely limited alternatives to access chemotherapy and radiotherapy during these years, may be important factors to explain the difference in the impact of permits delays/denials between the two study periods.

BackgroundResearch has questioned the safety of delaying or withholding antibiotics for suspected urinary tract infection (UTI) in older patients. We evaluated the association between antibiotic treatment for lower UTI and risk of bloodstream infection (BSI) in adults aged ≥65 years in primary care.Methods and findingsWe analyzed primary care records from patients aged ≥65 years in England with community-onset UTI using the Clinical Practice Research Datalink (2007-2015) linked to Hospital Episode Statistics and census data. The primary outcome was BSI within 60 days, comparing patients treated immediately with antibiotics and those not treated immediately. Crude and adjusted associations between exposure and outcome were estimated using generalized estimating equations. A total of 147,334 patients were included representing 280,462 episodes of lower UTI. BSI occurred in 0.4% (1,025/244,963) of UTI episodes with immediate antibiotics versus 0.6% (228/35,499) of episodes without immediate antibiotics. After adjusting for patient demographics, year of consultation, comorbidities, smoking status, recent hospitalizations, recent accident and emergency (A&E) attendances, recent antibiotic prescribing, and home visits, the odds of BSI were equivalent in patients who were not treated with antibiotics immediately and those who were treated on the date of their UTI consultation (adjusted odds ratio [aOR] 1.13, 95% CI 0.97-1.32, p-value = 0.105). Delaying or withholding antibiotics was associated with increased odds of death in the subsequent 60 days (aOR 1.17, 95% CI 1.09-1.26, p-value < 0.001), but there was limited evidence that increased deaths were attributable to urinary-source BSI. Limitations include overlap between the categories of immediate and delayed antibiotic prescribing, residual confounding underlying differences between patients who were/were not treated with antibiotics, and lack of microbiological diagnosis for BSI.ConclusionsIn this study, we observed that delaying or withholding antibiotics in older adults with suspected UTI did not increase patients' risk of BSI, in contrast with a previous study that analyzed the same dataset, but mortality was increased. Our findings highlight uncertainty around the risks of delaying or withholding antibiotic treatment, which is exacerbated by systematic differences between patients who were and were not treated immediately with antibiotics. Overall, our findings emphasize the need for improved diagnostic/risk prediction strategies to guide antibiotic prescribing for suspected UTI in older adults.

ObjectivesTo demonstrate how data-driven variability methods can be used to identify changes in disease recording in two English electronic health records databases between 2001 and 2015.DesignRepeated cross-sectional analysis that applied data-driven temporal variability methods to assess month-by-month changes in routinely collected medical data. A measure of difference between months was calculated based on joint distributions of age, gender, socioeconomic status and recorded cardiovascular diseases. Distances between months were used to identify temporal trends in data recording.Setting400 English primary care practices from the Clinical Practice Research Datalink (CPRD GOLD) and 451 hospital providers from the Hospital Episode Statistics (HES).Main outcomesThe proportion of patients (CPRD GOLD) and hospital admissions (HES) with a recorded cardiovascular disease (CPRD GOLD: coronary heart disease, heart failure, peripheral arterial disease, stroke; HES: International Classification of Disease codes I20-I69/G45).ResultsBoth databases showed gradual changes in cardiovascular disease recording between 2001 and 2008. The recorded prevalence of included cardiovascular diseases in CPRD GOLD increased by 47%–62%, which partially reversed after 2008. For hospital records in HES, there was a relative decrease in angina pectoris (−34.4%) and unspecified stroke (−42.3%) over the same time period, with a concomitant increase in chronic coronary heart disease (+14.3%). Multiple abrupt changes in the use of myocardial infarction codes in hospital were found in March/April 2010, 2012 and 2014, possibly linked to updates of clinical coding guidelines.ConclusionsIdentified temporal variability could be related to potentially non-medical causes such as updated coding guidelines. These artificial changes may introduce temporal correlation among diagnoses inferred from routine data, violating the assumptions of frequently used statistical methods. Temporal variability measures provide an objective and robust technique to identify, and subsequently account for, those changes in electronic health records studies without any prior knowledge of the data collection process.

Behaviour change is key to combating antimicrobial resistance. Antimicrobial stewardship (AMS) programmes promote and monitor judicious antibiotic use, but there is little consideration of behavioural and social influences when designing interventions. We outline a programme of research which aims to co-design AMS interventions across healthcare settings, by integrating data-science, evidence- synthesis, behavioural-science and user-centred design. The project includes three work-packages (WP): WP1 (Identifying patterns of prescribing): analysis of electronic health-records to identify prescribing patterns in care-homes, primary-care, and secondary-care. An online survey will investigate consulting/antibiotic-seeking behaviours in members of the public. WP2 (Barriers and enablers to prescribing in practice): Semi-structured interviews and observations of practice to identify barriers/enablers to prescribing, influences on antibiotic-seeking behaviour and the social/contextual factors underpinning prescribing. Systematic reviews of AMS interventions to identify the components of existing interventions associated with effectiveness. Design workshops to identify constraints influencing the form of the intervention. Interviews conducted with healthcare-professionals in community pharmacies, care-homes, primary-, and secondary-care and with members of the public. Topic guides and analysis based on the Theoretical Domains Framework. Observations conducted in care-homes, primary and secondary-care with analysis drawing on grounded theory. Systematic reviews of interventions in each setting will be conducted, and interventions described using the Behaviour Change Technique taxonomy v1. Design workshops in care-homes, primary-, and secondary care. WP3 (Co-production of interventions and dissemination). Findings will be integrated to identify opportunities for interventions, and assess whether existing interventions target influences on antibiotic use. Stakeholder panels will be assembled to co-design and refine interventions in each setting, applying the Affordability, Practicability, Effectiveness, Acceptability, Side-effects and Equity (APEASE) criteria to prioritise candidate interventions. Outputs will inform development of new AMS interventions and/or optimisation of existing interventions. We will also develop web-resources for stakeholders providing analyses of antibiotic prescribing patterns, prescribing behaviours, and evidence reviews.

Abstract Background Renal impairment (RI) is a negative prognostic factor in Multiple Myeloma (MM) and affected patients are often excluded from autologous stem cell transplantation (ASCT). However, it remains unclear whether historically inferior outcome data still hold true. Methods From a total of 475 eligible MM patients who had undergone ASCT between 1998 and 2016, 374 were included in this multi-centric retrospective cohort study. Renal function was determined both at the time of MM diagnosis and ASCT by estimated glomerular filtration rate (eGFR according to the MDRD formula, RI defined as eGFR

Objectives To investigate the risk of adverse outcomes following discordant antibiotic treatment (urinary organism resistant) for culture-confirmed community-onset lower urinary tract infection (UTI). Methods Cohort study using routinely collected linked primary care, secondary care and microbiology data from patients with culture-confirmed community-onset lower UTI (COLUTI). Antibiotic treatment within ±3 days was considered concordant if the urinary organism was sensitive and discordant if resistant. The primary outcome was the proportion of patients experiencing urinary infection-related hospital admission (UHA) within 30 days. Secondary outcomes were the proportion of patients experiencing reconsultation within 30 days, and the odds of UHA and reconsultation following discordant treatment, adjusting for sex, age, risk factors for complicated UTI, previous antibiotic treatment, recurrent UTI and comorbidities. Results A total of 11 963 UTI episodes in 8324 patients were included, and 1686 episodes (14.1%, 95% CI 13.5%–14.7%) were discordant. UHA occurred in 212/10 277 concordant episodes (2.1%, 95% CI 1.8%–2.4%) and 88/1686 discordant episodes (5.2%, 95% CI 4.2%–6.4%). Reconsultation occurred in 3961 concordant (38.5%, 95% CI 37.6%–39.5%) and 1472 discordant episodes (87.3%, 95% CI 85.6%–88.8%). Discordant treatment compared with concordant was associated with increased odds of UHA (adjusted OR 2.31, 95% CI 1.77–3.0, P < 0.001) and reconsultation (adjusted OR 11.25, 95% CI 9.66–13.11, P < 0.001) on multivariable analysis. Chronic kidney disease and diabetes mellitus were also independently associated with increased odds of UHA. Conclusions One in seven COLUTI episodes in primary care were treated with discordant antibiotics. In higher risk patients requiring urine culture, empirical antibiotic choice optimization could meaningfully reduce adverse outcomes. [ABSTRACT FROM AUTHOR]