Quality of Care

1.
Specialist nursing support for unpaid carers of people with dementia: a mixed-methods feasibility study.
Editors
Gridley K1, Aspinal F1, Parker G1, Weatherly H2, Faria R2, Longo F2, van den Berg B2.

Source
Southampton (UK): NIHR Journals Library; 2019 Mar.
Health Services and Delivery Research.

Author information
Excerpt
BACKGROUND:
Unpaid carers are the mainstay of support for people with dementia. Admiral Nursing (AN) is the only specialist nursing service that specifically focuses on supporting such carers, but evidence of its effectiveness, costs and relationships with other health and social care services is limited. This project aimed to address this gap and explore the feasibility of a full-scale formal evaluation.

OBJECTIVES:
To explore the relationships between characteristics of carers and people with dementia, service type and input and outcomes; to develop and test data collection methods for subsequent economic evaluation; to explore the effect of AN on outcomes and costs, compared with usual care; to explore the perceived system-wide impact of specialist support for carers of people with dementia, compared with usual care; and to implement new data collection methods in AN, which could also be used by other services, to facilitate evaluation.

DESIGN:
A mixed-methods study, using secondary analysis of an administrative data set, and primary (cross-sectional) quantitative and qualitative data collection.

SETTING:
Qualitative research with carers in four areas of England; a survey of carers in 32 local authority areas (16 with and 16 without AN); and qualitative interviews with professionals in four areas.

PARTICIPANTS:
Thirty-five carers of people with dementia and 20 professionals were interviewed qualitatively; 346 carers completed in-scope questionnaires (46% through AN services and 54% from matched non-AN areas).

INTERVENTIONS:
Specialist nursing support for carers of people with dementia (with AN as an exemplar) compared with usual care.

MAIN OUTCOME MEASURES:
The Adult Social Care Outcomes Toolkit for Carers; the EuroQol-5 Dimensions, five-level version; and the Caregiver Self-Efficacy for Managing Dementia Scale.

DATA SOURCES:
Dementia UK’s AN administrative data set.

RESULTS:
Admiral Nurses are successfully targeting the most complex cases. They work predominantly with older carers who have the main responsibility for the person with dementia, who are heavily involved in caring activity and who may be at risk. Three outcome areas that are important to carers of people with dementia and are potentially affected by receiving support are (1) carer self-efficacy, (2) carer quality of life (3) and carer mental and physical health. The carers in the survey receiving support from AN were older, were more heavily involved in caring and had poorer outcomes than carers not in receipt of such support. When these differences were controlled for, carers supported by AN had better outcomes, although the differences did not reach statistical significance. Health and social care costs were similar in both groups. The perceived system-wide impact of services, such as AN, is not well understood by professional stakeholders.

LIMITATIONS:
Challenges were experienced in identifying similar carers in areas with or without an AN service and in the cross-sectional nature of the work.

CONCLUSIONS:
Specialist nursing support to carers of people with dementia may enable them to continue providing care to the end or very close to the end of the dementia journey. The outcomes for such carers may be no different from, or even slightly better than, those of similar carers without this support, although the costs to health and social care services are the same in each case.

FUTURE WORK:
Future research could investigate the impact of specialist support for carers on admission to long-term care. There is also a need for more work to encourage routine use of the selected outcome measures in dementia service delivery.

FUNDING:
The National Institute for Health Research Health Services and Delivery Research programme.

Copyright © Queen’s Printer and Controller of HMSO 2019. This work was produced by Gridley et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

Sections
Plain English summary
Scientific summary
Chapter 1. Introduction
Chapter 2. Study design and methods
Chapter 3. Analysis of the Admiral Nursing administrative data set
Chapter 4. The outcomes of carer support and development of the carer questionnaire (work package 2)
Chapter 5. Analysis of the survey of carers of people with dementia
Chapter 6. Exploratory analysis of the outcomes and the costs of Admiral Nursing compared with those of usual care
Chapter 7. Understanding the wider impact of specialist support for carers of people with dementia
Chapter 8. Discussion and conclusions
Acknowledgements
References
Appendix 1. Work packages 5 and 6: ensuring that the study findings inform future research and practice
Appendix 2. Support for the carers of people with dementia survey
Appendix 3. Tables and figures
Appendix 4. Analysis from Chapter 5
Appendix 5. Analysis from Chapter 6
List of abbreviations
PMID: 30916917
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Specialist nursing support for unpaid carers of people with dementia: a mixed-methods feasibility study
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Select item 30917286
2.
Ann Am Thorac Soc. 2019 Mar 27. doi: 10.1513/AnnalsATS.201812-847IP. [Epub ahead of print]
The Future of Critical Care Lies in Quality Improvement and Education.
Niven AS1, Herasevich S2, Pickering BW3, Gajic O2.
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Abstract
N/A (Innovation and Provocation Section).

PMID: 30917286 DOI: 10.1513/AnnalsATS.201812-847IP
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Select item 30917161
3.
PLoS One. 2019 Mar 27;14(3):e0214049. doi: 10.1371/journal.pone.0214049. eCollection 2019.
Spatial and socio-economic correlates of effective contraception among women seeking post-abortion care in healthcare facilities in Kenya.
Mutua MM1,2, Achia TNO2,3, Manderson L2,4, Musenge E2.
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Abstract
INTRODUCTION:
Information, counseling, availability of contraceptives, and their adoption by post-abortion care (PAC) patients are central to the quality of PAC in healthcare facilities. Effective contraceptive adoption by these patients reduces the risks of unintended pregnancy and repeat abortion.

METHODS:
This study uses data from the Incidence and Magnitude of Unsafe Abortion Study of 2012 to assess the level and determinants of highly effective contraception among patients treated with complications from an unsafe abortion in healthcare facilities in Kenya. Highly effective contraception was defined as any method adopted by a PAC patient that reduces pregnancy rate by over 99%.

RESULTS:
Generally, contraceptive counseling was high among all PAC patients (90%). However, only 54% of them received a modern family planning method-45% a short-acting method and 9% a long-acting and permanent method. Adoption of highly effective contraception was determined by patient’s previous exposure to unintended pregnancies, induced abortion and modern family planning (FP). Facility level factors associated with the uptake of highly effective contraceptives included: facility ownership, availability of evacuation procedure room, whether the facility had a specialized obstetric-gynecologist, a facility that also had maternity services and the number of FP methods available for PAC patients.

DISCUSSION AND CONCLUSION:
For better adoption of highly effective FP, counseling of PAC patients requires an understanding of the patient’s past experience with contraception and their future fertility intentions and desires in order to meet their reproductive needs more specifically. Family planning integration with PAC can increase contraceptive uptake and improve the reproductive health of post-abortion care patients.

PMID: 30917161 DOI: 10.1371/journal.pone.0214049
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Select item 30917097
4.
Health Technol Assess. 2019 Mar;23(13):1-226. doi: 10.3310/hta23130.
Three biomarker tests to help diagnose preterm labour: a systematic review and economic evaluation.
Varley-Campbell J1, Mújica-Mota R1, Coelho H1, Ocean N1, Barnish M1, Packman D1, Dodman S1, Cooper C1, Snowsill T1,2, Kay T3, Liversedge N3, Parr M4, Knight L3, Hyde C1, Shennan A5,6, Hoyle M1.
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Abstract
BACKGROUND:
Preterm birth may result in short- and long-term health problems for the child. Accurate diagnoses of preterm births could prevent unnecessary (or ensure appropriate) admissions into hospitals or transfers to specialist units.

OBJECTIVES:
The purpose of this report is to assess the test accuracy, clinical effectiveness and cost-effectiveness of the diagnostic tests PartoSure™ (Parsagen Diagnostics Inc., Boston, MA, USA), Actim® Partus (Medix Biochemica, Espoo, Finland) and the Rapid Fetal Fibronectin (fFN)® 10Q Cassette Kit (Hologic, Inc., Marlborough, MA, USA) at thresholds ≠50 ng/ml [quantitative fFN (qfFN)] for women presenting with signs and symptoms of preterm labour relative to fFN at 50 ng/ml.

METHODS:
Systematic reviews of the published literature were conducted for diagnostic test accuracy (DTA) studies of PartoSure, Actim Partus and qfFN for predicting preterm birth, the clinical effectiveness following treatment decisions informed by test results and economic evaluations of the tests. A model-based economic evaluation was also conducted to extrapolate long-term outcomes from the results of the diagnostic tests. The model followed the structure of the model that informed the 2015 National Institute for Health and Care Excellence guidelines on preterm labour diagnosis and treatment, but with antenatal steroids use, as opposed to tocolysis, driving health outcomes.

RESULTS:
Twenty studies were identified evaluating DTA against the reference standard of delivery within 7 days and seven studies were identified evaluating DTA against the reference standard of delivery within 48 hours. Two studies assessed two of the index tests within the same population. One study demonstrated that depending on the threshold used, qfFN was more or less accurate than Actim Partus, whereas the other indicated little difference between PartoSure and Actim Partus. No study assessing qfFN and PartoSure in the same population was identified. The test accuracy results from the other included studies revealed a high level of uncertainty, primarily attributable to substantial methodological, clinical and statistical heterogeneity between studies. No study compared all three tests simultaneously. No clinical effectiveness studies evaluating any of the three biomarker tests were identified. One partial economic evaluation was identified for predicting preterm birth. It assessed the number needed to treat to prevent a respiratory distress syndrome case with a ‘treat-all’ strategy, relative to testing with qualitative fFN. Because of the lack of data, our de novo model involved the assumption that management of pregnant women fully adhered to the results of the tests. In the base-case analysis for a woman at 30 weeks’ gestation, Actim Partus had lower health-care costs and fewer quality-adjusted life-years (QALYs) than qfFN at 50 ng/ml, reducing costs at a rate of £56,030 per QALY lost compared with qfFN at 50 ng/ml. PartoSure is less costly than Actim Partus while being equally effective, but this is based on diagnostic accuracy data from a small study. Treatment with qfFN at 200 ng/ml and 500 ng/ml resulted in lower cost savings per QALY lost relative to fFN at 50 ng/ml than treatment with Actim Partus. In contrast, qfFN at 10 ng/ml increased QALYs, by 0.002, and had a cost per QALY gained of £140,267 relative to fFN at 50 ng/ml. Similar qualitative results were obtained for women presenting at different gestational ages.

CONCLUSION:
There is a high degree of uncertainty surrounding the test accuracy and cost-effectiveness results. We are aware of four ongoing UK trials, two of which plan to enrol > 1000 participants. The results of these trials may significantly alter the findings presented here.

STUDY REGISTRATION:
The study is registered as PROSPERO CRD42017072696.

FUNDING:
The National Institute for Health Research Health Technology Assessment programme.

PLAIN-LANGUAGE-SUMMARY:
Infants may suffer from health problems if they are born early. If a mother has symptoms of labour before her baby is due, a test could be used to predict if the symptoms are real or a false alarm. A test could help the doctor to decide whether the mother needs treatment or to move to a specialist hospital or if she could be sent home (if it is a false alarm). Our report compares three tests [PartoSure™ (Parsagen Diagnostics Inc., Boston, MA, USA), Actim® Partus (Medix Biochemica, Espoo, Finland) and the Fetal Fibronectin (fFN) Test (Hologic, Inc., Marlborough, MA, USA)] on how well they predict an early birth and how the costs and the long-term health outcomes of the child compare between and among tests. All the published literature reporting the accuracy of the three tests and their costs was reviewed. We developed a new cost-effectiveness model, which estimated the long-term health outcomes of the child based on the test results. Twenty of the studies reviewed looked at how good the tests were at predicting an early birth within the next 7 days, and six looked at predicting birth within 48 hours. The designs of the studies and the women taking part in the studies varied greatly. This meant that comparing the accuracy of the tests was very difficult and it would be unfair to decide which test was the best. Our model suggested no firm conclusions for the cost-effectiveness of fFN compared with Actim Partus. PartoSure appears to be less costly than Actim Partus and equally good at predicting preterm birth, but this is based on a study of very few patients. There were no data that allowed us to compare all three tests together. The accuracy of the results is uncertain, mainly because all the studies are very different. We are aware of four related UK trials that are currently ongoing that plan to include large numbers of women.

KEYWORDS:
ACTIM PARTUS; FETAL FIBRONECTIN; PAMG-1; PARTOSURE; PH(IGFBP-1); PHOSPHORYLATED INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN; PLACENTAL ALPHA MACROGLOBULIN-1; TEST ACCURACY

PMID: 30917097 DOI: 10.3310/hta23130
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Select item 30917079
5.
J Manag Care Spec Pharm. 2019 Apr;25(4):490-498. doi: 10.18553/jmcp.2019.25.4.490.
The Impact of Price Reductions After Loss of Exclusivity in a Cost-Effectiveness Analysis: Fingolimod Versus Interferon Beta-1a for the Treatment of Relapsing-Remitting Multiple Sclerosis.
Hua LH1, Hersh CM1, Morten P2, Kusel J2, Lin F3, Cave J3, Varga S4, Herrera V3, Ko JJ3.
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Abstract
BACKGROUND:
Cost-effectiveness analyses tend not to take into account the availability of lower-priced generics following loss of exclusivity (LOE) of branded products. By not considering these generics, which are typically adopted quickly, total costs are likely to be overestimated and may be unreflective of real-world payer conditions in the United States.

OBJECTIVE:
To assess the impact of including future price reductions following LOE on the cost-effectiveness of fingolimod versus intramuscularly administered interferon beta-1a (IM IFNβ-1a) as treatments for multiple sclerosis.

METHODS:
This model was adopted from a previously published Markov model and was conducted from a U.S. payer perspective over a 10-year time horizon. Patients with relapsing-remitting multiple sclerosis entered the model and received either fingolimod (an oral therapy) or IM IFNβ-1a (an injectable). These treatments reflect the interventions studied in the TRANSFORMS randomized clinical trial. Clinical, cost, and utility inputs were based on a recent cost-effectiveness review of therapies for multiple sclerosis. To model LOE, price reductions and the proportion of patients switching to generic versions following LOE were based on published estimates. Price reductions varied to reflect the difference in product types (oral vs. large molecule injectable). Assumptions were also made around the proportion of patients switching to generic versions over time following LOE and the projected date of LOE. Outcomes included per-patient total direct costs (medication, administration and monitoring, and disease-related costs including relapses), quality-adjusted life-years, and the incremental cost per quality-adjusted life-year.

RESULTS:
Assuming no price reductions following LOE, fingolimod was considered cost-effective versus IM IFNβ-1a ($118,434 per quality-adjusted life-year), despite having higher total direct costs over 10 years ($475,740 vs. $446,792). When including future price reductions following LOE, total direct costs were reduced with fingolimod and were lower than those accrued with IM IFNβ-1a over the model time horizon ($308,570 vs. $442,653). Cost-effectiveness results were sensitive to changes in both clinical parameters and medication costs. Scenario analyses demonstrated that an earlier date of LOE was associated with lower total costs.

CONCLUSIONS:
Health economic models may predict higher total costs when the price reductions following LOE are not considered. Here, oral fingolimod was seen to be cost-saving versus IM IFNβ-1a over the model time horizon when such price reductions were included. The cost implications of not accounting for future price changes may determine whether an intervention is considered cost-effective and as such may influence reimbursement decisions based on cost-effectiveness thresholds. Multiple product types (e.g., oral, injectable, and infused agents) have been approved for use as treatments for multiple sclerosis in the United States, and LOE is likely to have a different effect on each of these therapies.

DISCLOSURES:
This study was funded by Novartis Pharmaceuticals Corporation. Hua and Hersh report consulting fees from Novartis for work on this study. Hua also reports speaking, advisory board, and consulting fees from Biogen, Genzyme, Teva, EMD Serono, Genentech, TG Therapeutics, and Novartis for activities outside of this study. Hersh also reports speaking and consulting fees from Novartis, Biogen, Genzyme, Genentech, and EMD Serono for activities outside of this study, and research grants from PCORI and Biogen. At the time of this research, Morten and Kusel were paid employees of Costello Medical, which was contracted by Novartis to undertake some of this study’s work. Lin, Cave, Herrera, and Ko were paid employees of Novartis at the time of this research. Cave, Herrera, and Ko also report owning stock in Novartis Pharmaceuticals. Varga provided services to Novartis at the time of this research and has nothing further to disclose. This research was presented as a poster at the AMCP Managed Care & Specialty Pharmacy Annual Meeting 2017; March 27-30, 2017; Denver, CO.

PMID: 30917079 DOI: 10.18553/jmcp.2019.25.4.490
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6.
J Crohns Colitis. 2019 Mar 27. pii: jjz003. doi: 10.1093/ecco-jcc/jjz003. [Epub ahead of print]
The Evolution of Health Care Utilisation and Costs for Inflammatory Bowel Disease Over Ten Years.
Pillai N1, Dusheiko M1,2,3, Maillard MH4,5, Rogler G6, Brüngger B7, Bähler C7, Pittet VEH1; Swiss IBD Cohort Study Group.
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Abstract
BACKGROUND AND AIMS:
Inflammatory bowel disease [IBD] places an economic strain on health systems due to expensive pharmaceutical therapy, risk of hospitalisation and surgery, and long-term monitoring. The evolving treatment guidelines advocate rapid scale-up to biologic agents in order to improve health outcomes and quality of life. This study evaluated changes in health care utilisation and expenditures for IBD in Switzerland over time.

METHODS:
We extracted clinical, patient, and resource consumption data from the Swiss IBD Cohort Study between 2006 and 2016. Average unit costs for IBD-related events were derived from Swiss claims data and pharmaceutical price lists. We used multivariate regression, controlling for patient-level characteristics, to estimate trends and determinants of direct and indirect costs and resource utilisation.

RESULTS:
We included 2365 adults diagnosed with Crohn’s disease [CD; N = 1353] and ulcerative colitis [UC; N = 1012]. From 2006-16, mean health care expenditures per patient per year were 9504 euros [70% drugs, 23% inpatient, 7% outpatient] for CD and 5704 euros [68% drugs, 22% inpatient, 10% outpatient] for UC. Health care costs increased by 7% [CD] and 10% [UC] per year, largely due to rising pharmaceutical expenditures driven by increased biologic agent use. Inpatient, outpatient, and indirect costs fluctuated and did not offset increased pharmaceutical costs. Disease characteristics were important predictors of costs.

CONCLUSIONS:
Increased expenditure for IBD was marked by a shift towards greater pharmaceutical management over the past decade. This study highlights the need to identify cost-effective treatment strategies in the face of increased uptake and expenditures associated with innovative treatments.

Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions.

KEYWORDS:
Crohn’s disease; IBD; health economics; ulcerative colitis

PMID: 30916775 DOI: 10.1093/ecco-jcc/jjz003
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Select item 30916758
7.
Age Ageing. 2019 Mar 22. pii: afz025. doi: 10.1093/ageing/afz025. [Epub ahead of print]
Can comprehensive geriatric assessment be delivered without the need for geriatricians? A formative evaluation in two perioperative surgical settings.
Kocman D1, Regen E1, Phelps K1, Martin G2, Parker S3, Gilbert T4, Conroy S1.
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Abstract
INTRODUCTION:
the aim of this study was to design an approach to improving care for frail older patients in hospital services where comprehensive geriatric assessment (CGA) was not part of the clinical tradition.

METHODS:
the intervention was based on the principles of CGA, using quality improvement methodology to embed care processes. Qualitative methods and coproduction were used to inform development of the intervention, which was directed towards the health care professionals involved in peri-operative/surgical cancer care pathways in two large UK teaching hospitals. A formative, qualitative evaluation was undertaken; data collection and analysis were guided by normalisation process theory.

RESULTS:
the clinicians involved agreed to use the toolkit, identifying potential benefits including improved surgical decision making and delivery of interventions pre-operatively. However, sites concluded that pre-operative assessment was not the best place for CGA, and at the end of the 12-month trial, implementation was still nascent. Efforts competed against the dominance of national time-limited targets, and concerns relating to patients’ immediate treatment and recovery. Some participants involved in the peri-operative pathway felt that CGA required ongoing specialist input from geriatricians, but it was not clear that this was sustainable.

CONCLUSIONS:
clinical toolkits designed to empower non-geriatric teams to deliver CGA were received with initial enthusiasm, but did not fully achieve their stated aims due to the need for an extended period of service development with geriatrician support, competing priorities, and divergent views about appropriate professional domains.

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Geriatrics Society.

KEYWORDS:
acute care; comprehensive ; frailty; geriatric assessment; older people; qualitative research; quality improvement

PMID: 30916758 DOI: 10.1093/ageing/afz025
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Select item 30916666
8.
J Med Internet Res. 2019 Mar 27;21(3):e10831. doi: 10.2196/10831.
Online Health Information Seeking and eHealth Literacy Among Patients Attending a Primary Care Clinic in Hong Kong: A Cross-Sectional Survey.
Wong DK1, Cheung MK1.
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Abstract
BACKGROUND:
Previous studies have suggested that patients’ online health information seeking affects their medical consultations and patient-doctor relationships. An up-to-date picture of patients’ online health information-seeking behaviors can inform and prepare frontline health care professionals to collaborate, facilitate, or empower their patients to access and manage health information found online.

OBJECTIVE:
This study explores the prevalence, patterns, and predictors of online health information-seeking behaviors among primary care patients in Hong Kong, and the relations between online health information seeking and electronic health (eHealth) literacy.

METHODS:
Patients attending a university primary care clinic in Hong Kong were asked to complete a questionnaire survey on their demographic backgrounds; health status; frequency and pattern of online health information seeking; contents, sources, and reasons for online health information seeking; and their eHealth literacy. eHealth literacy was measured by the validated eHealth Literacy Scale (eHEALS). Regression analyses explored various demographic and behavioral predictors to online health information seeking, and predictors to eHealth literacy.

RESULTS:
In all, 97.32% (1162/1194) respondents used the internet, of which 87.44% (1016/1162) had used the internet to find health information. Most respondents (65.97%, 665/1008) searched once monthly or more. Few (26.88%, 271/1008) asked their doctor about health information found online, but most doctors (56.1%, 152/271) showed little or no interest at all. The most sought topic was symptom (81.59%, 829/1016), the top reason was noticing new symptoms or change in health (70.08%, 712/1016), the most popular source was online encyclopedia (69.98%, 711/1016), and the top reason for choosing a source was convenience (55.41%, 563/1016). Poisson regression analysis identified high eHEALS score, fair or poor self-rated health, having a chronic medical condition, and using the internet several times a day as significant predictors of online health information seeking. Multiple regression analysis identified lower age, better self-rated health, more frequent internet use, more frequent online health information seeking, and more types of health information sought as significant predictors to higher eHealth literacy.

CONCLUSIONS:
Online health information seeking is prevalent among primary care patients in Hong Kong, but only a minority shared the information with doctors. Websites were chosen more for convenience than for accuracy or authoritativeness. Doctors should recognize patients’ online health information-seeking behavior, and facilitate and empower them to search for high-quality online health information.

©David Ka-Ki Wong, Man-Kuen Cheung. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 27.03.2019.

KEYWORDS:
Hong Kong; eHealth literacy; online health information seeking; primary care

PMID: 30916666 DOI: 10.2196/10831
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9.
JMIR Mhealth Uhealth. 2019 Mar 27;7(3):e12284. doi: 10.2196/12284.
Mobile Phone-Based Use of the Photoplethysmography Technique to Detect Atrial Fibrillation in Primary Care: Diagnostic Accuracy Study of the FibriCheck App.
Proesmans T#1, Mortelmans C#2, Van Haelst R2, Verbrugge F1, Vandervoort P1, Vaes B2.
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Abstract
BACKGROUND:
Mobile phone apps using photoplethysmography (PPG) technology through their built-in camera are becoming an attractive alternative for atrial fibrillation (AF) screening because of their low cost, convenience, and broad accessibility. However, some important questions concerning their diagnostic accuracy remain to be answered.

OBJECTIVE:
This study tested the diagnostic accuracy of the FibriCheck AF algorithm for the detection of AF on the basis of mobile phone PPG and single-lead electrocardiography (ECG) signals.

METHODS:
A convenience sample of patients aged 65 years and above, with or without a known history of AF, was recruited from 17 primary care facilities. Patients with an active pacemaker rhythm were excluded. A PPG signal was obtained with the rear camera of an iPhone 5S. Simultaneously, a single‑lead ECG was registered using a dermal patch with a wireless connection to the same mobile phone. PPG and single-lead ECG signals were analyzed using the FibriCheck AF algorithm. At the same time, a 12‑lead ECG was obtained and interpreted offline by independent cardiologists to determine the presence of AF.

RESULTS:
A total of 45.7% (102/223) subjects were having AF. PPG signal quality was sufficient for analysis in 93% and single‑lead ECG quality was sufficient in 94% of the participants. After removing insufficient quality measurements, the sensitivity and specificity were 96% (95% CI 89%-99%) and 97% (95% CI 91%-99%) for the PPG signal versus 95% (95% CI 88%-98%) and 97% (95% CI 91%-99%) for the single‑lead ECG, respectively. False-positive results were mainly because of premature ectopic beats. PPG and single‑lead ECG techniques yielded adequate signal quality in 196 subjects and a similar diagnosis in 98.0% (192/196) subjects.

CONCLUSIONS:
The FibriCheck AF algorithm can accurately detect AF on the basis of mobile phone PPG and single-lead ECG signals in a primary care convenience sample.

©Tine Proesmans, Christophe Mortelmans, Ruth Van Haelst, Frederik Verbrugge, Pieter Vandervoort, Bert Vaes. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 27.03.2019.

KEYWORDS:
algorithm; atrial fibrillation; electrocardiography; mobile phone; photoplethysmography

PMID: 30916656 DOI: 10.2196/12284
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Select item 30916629
10.
J Urol. 2019 Mar 27:101097JU0000000000000250. doi: 10.1097/JU.0000000000000250. [Epub ahead of print]
Clustering of Patients with Interstitial Cystitis/Bladder Pain Syndrome and Chronic Prostatitis/Chronic Pelvic Pain Syndrome.
Lai HH1,2, Thu JHL1, Moh FV1, Paradis A1, Vetter J1.
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Abstract
AIMS:
To use clustering analysis of patient symptoms to discover common patient subtypes in females and males with interstitial cystitis/bladder pain syndrome (IC/BPS) or chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

METHODS:
Clinical variables included in the k-means clustering included the severity of urologic pain (0-10 numeric rating scale, NRS), urinary urgency (0-10 NRS), frequency (0-10 NRS), non-urologic pain (0-10 NRS), and either a yes or no to each of the six UPOINT domains.

RESULTS:
211 UCPPS patients seeking care of their IC/BPS or CP/CPPS were included. K-means clustering algorithm identified 3 clusters of IC/BPS and CP/CPPS patients: (1) a mild pelvic symptom cluster in about 30% of patients; (2) a severe pelvic symptom cluster in about 40% of patients; and (3) a systemic symptom cluster in about 30% of patients. Patients in the systemic cluster were younger (by about 5-7 years), more likely to be female, had the most severe urinary symptoms (urgency, frequency, painful bladder filling), the most severe pelvic pain and non-pelvic pain. They were also more likely to have chronic overlapping pain conditions (COPCs), psychosocial issues (depression, anxiety, somatic symptoms), and poorer quality of life than the two other pelvic clusters. They were not less likely to have Hunner lesions inside the bladder.

CONCLUSIONS:
Symptom-based clustering has identified 3 clusters of IC/BPS and CP/CPPS patients. These patient subtypes have different pelvic and systemic presentation. Patients within the systemic cluster may benefit from interdisciplinary therapies. Future studies to elucidate the differences in pathophysiology among these clusters are needed.

KEYWORDS:
Hunner lesions; chronic prostatitis;urologic chronic pelvic pain syndrome; clinical subtypes; clustering; interstitial cystitis; phenotypes

PMID: 30916629 DOI: 10.1097/JU.0000000000000250
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Select item 30916615
11.
Palliat Med. 2019 Mar 27:269216319839635. doi: 10.1177/0269216319839635. [Epub ahead of print]
Appropriate frameworks for economic evaluation of end of life care: A qualitative investigation with stakeholders.
Kinghorn P1, Coast J2.
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Abstract
BACKGROUND::
The use of quality-adjusted life years rests on the assertion that the objective of the health care system is to improve health.

AIM::
To elicit the views of expert stakeholders on the purpose and evaluation of supportive end of life care, and explore how different purposes of end of life care imply the need for different evaluative frameworks.

DESIGN::
Semi-structured qualitative interviews, analysed through an economic lens using a constant comparative approach.

PARTICIPANTS::
Twenty professionals working in or visiting the United Kingdom or Republic of Ireland, with clinical experience and/or working as academics in health-related disciplines.

RESULTS::
Four purposes of end of life care were identified from and are critiqued with the aid of the qualitative data: to improve health, to enable patients to die in their preferred place, to enable the patient to experience a good death, and to enable the patient to experience a good death, and those who are close to the patient to have an experience which is as free as possible from fear, stress and distress.

CONCLUSION::
Managing symptoms and reducing anxiety were considered to be core objectives of end of life care and fit with the wider health service objective of improving/maximising health. A single objective across the entire health system ensures consistency in the way that resource allocation is informed across that entire system. However, the purpose of care at the end of life is more complex, encompassing diverse and patient-centred objectives which we have interpreted as enabling the patient to experience a good death.

KEYWORDS:
Palliative care; a good death; economic evaluation; place of death; quality-adjusted life years; terminal care

PMID: 30916615 DOI: 10.1177/0269216319839635
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Select item 30916510
12.
Harefuah. 2019 Mar;158(3):196-199.
[TREATMENT OF IMMUNE THROMBOCYTOPENIC PURPURA IN ADULTS: UPDATE].
[Article in Hebrew]
Blickstein D1.
Author information
Abstract
Primary immune thrombocytopenic purpura (ITP) is an acquired immune-mediated disorder characterized by isolated thrombocytopenia (platelet count less than 100X109/L), caused by IgG autoantibodies which bind to platelets and megakaryocyte, T cell-mediated platelet destruction and impaired megakaryocytic function. Symptoms can manifest as petechiae, purpura, mucosal bleeding and rarely fatal intracranial hemorrhage, as well as reduced quality of life. A wide range of bleeding manifestations exists and it is impossible to tell who will bleed, when and where. The goal of treatment is to prevent severe/life-threatening bleeding. Treatment modalities target various aspects of ITP pathophysiology such as the inhibition of autoantibody production (decreased autoimmune process), modulation of T cell activity (with prolongation of platelets survival), and stimulation of platelet production. The American Society of Hematology and the International Society of Thrombosis and Hemostasis published guidelines on the treatment of ITP patients, where first line treatment focuses on inhibition of autoantibody production and platelet degradation, second-line treatments include immunosuppressive drugs and splenectomy, and third-line treatments aim to stimulate platelet production by megakaryocytes. New available strategies might change the order of treatment lines. As in other situations, treatment should be tailored according to the patient’s age, life style, comorbidities and compliance.

PMID: 30916510
Publication types
Select item 30916456
13.
Pediatr Blood Cancer. 2019 Mar 27:e27728. doi: 10.1002/pbc.27728. [Epub ahead of print]
Gender-specific differences in parental health-related quality of life in childhood cancer.
Rensen N1,2, Steur LM1, Schepers SA2,3, Merks JH2,4, Moll AC5, Kaspers GJ1,2, Grootenhuis MA2,3, van Litsenburg RR1,2.
Author information
Abstract
BACKGROUND:
Parents of children with cancer are at risk for impaired health-related quality of life (HRQoL). Most prior research has focused on the HRQoL of mothers. The aim of this study is to describe HRQoL in mothers and fathers, and determine the influence of sociodemographic, medical, and psychosocial factors.

PROCEDURE:
In a cross-sectional study, both parents completed questionnaires on sociodemographics, distress, and HRQoL. Parental HRQoL was compared to healthy population values. Differences between mothers and fathers were evaluated with multilevel analysis. Gender-specific HRQoL determinants were assessed via multiple linear regression analysis.

RESULTS:
Parents (202 mothers, 150 fathers; comprising 121 couples) of 231 children with different cancer diagnoses (mean time since diagnosis 3.3 ± 1.4 years, 90% posttreatment) participated. Compared to healthy women and men, mothers and fathers reported significantly impaired HRQoL on the following domains: cognitive functioning, sleep, daily activities, and vitality (Cohen’s d = 0.3-0.9). Additionally, maternal HRQoL was reduced on the domains gross motor functioning, pain, social functioning, sexuality, and depressive emotions. Mothers scored worse than fathers on six of 12 domains. Risk factors for adverse outcomes in both parents were higher distress, emotional and parenting problems, little social support, medication use, and active treatment of the child. Other determinants in mothers were non-Dutch background and unemployment, while lower HRQoL in fathers was predicted by their child’s diagnosis type, shorter time since diagnosis, and treatment intensity.

CONCLUSION:
These outcomes illustrate the need for family-centered care. Future interventions aimed at improving parental functioning should take into account gender-specific differences in HRQoL to reach optimal efficacy.

© 2019 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.

KEYWORDS:
cancer; child; oncology; parents; psychological stress; quality of life

PMID: 30916456 DOI: 10.1002/pbc.27728
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Select item 30916392
14.
Health Serv Res. 2019 Mar 27. doi: 10.1111/1475-6773.13137. [Epub ahead of print]
Impact of pediatric cardiac surgery regionalization on health care utilization and mortality.
Sakai-Bizmark R1,2,3, Mena LA1, Kumamaru H4, Kawachi I5, Marr EH1, Webber EJ1, Seo HH1,6, Friedlander SIM1, Chang RR1,2,3.
Author information
Abstract
OBJECTIVE:
Regionalization directs patients to high-volume hospitals for specialized care. We investigated regionalization trends and outcomes in pediatric cardiac surgery.

DATA SOURCES/STUDY SETTING:
Statewide inpatient data from eleven states between 2000 and 2012.

STUDY DESIGN:
Mortality, length of stay (LOS), and cost were assessed using multivariable hierarchical regression with state and year fixed effects. Primary predictor was hospital case-volume, categorized into low-, medium-, and high-volume tertiles.

DATA COLLECTION/EXTRACTION METHODS:
We used Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) to select pediatric cardiac surgery discharges.

PRINCIPAL FINDINGS:
In total, 2841 (8.5 percent), 8348 (25.1 percent), and 22 099 (66.4 percent) patients underwent heart surgeries in low-, medium-, and high-volume hospitals. Mortality decreased over time, but remained higher in low- and medium-volume hospitals. High-volume hospitals had lower odds of mortality and cost than low-volume hospitals (odds ratio [OR] 0.59, P < 0.01, and relative risk [RR] 0.91, P < 0.01, respectively). LOS was longer for high- and medium-volume hospitals, compared to low-volume hospitals (high-volume: RR 1.18, P < 0.01; medium-volume: RR 1.05, P < 0.01).

CONCLUSIONS:
Regionalization reduced mortality and cost, indicating fewer complications, but paradoxically increased LOS. Further research is needed to explore the full impact on health care utilization.

© Health Research and Educational Trust.

KEYWORDS:
case-volume; health care utilization; mortality; pediatric cardiology

PMID: 30916392 DOI: 10.1111/1475-6773.13137
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Grant support
Select item 30916340
15.
Int Health. 2019 Mar 21. pii: ihz009. doi: 10.1093/inthealth/ihz009. [Epub ahead of print]
Providing oxygen to children and newborns: a multi-faceted technical and clinical assessment of oxygen access and oxygen use in secondary-level hospitals in southwest Nigeria.
Bakare AA1, Graham H1,2, Ayede AI1,3, Peel D4, Olatinwo O5, Oyewole OB1, Fowobaje KR1, Qazi S6, Izadnegahdar R7, Duke T2, Falade AG1,3.
Author information
Abstract
BACKGROUND:
Oxygen is an essential medical therapy that is poorly available globally. We evaluated the quality of oxygen therapy in 12 secondary-level Nigerian hospitals, including access to oxygen equipment, equipment functionality, healthcare worker knowledge and appropriateness of use.

METHODS:
We conducted a three-part evaluation of oxygen access and use involving: (1) facility assessment (including technical evaluation of oxygen equipment), (2) clinical audit (children and neonates admitted January 2014-December 2015) and (3) survey of healthcare worker training and experience on the clinical use of oxygen (November 2015).

RESULTS:
Oxygen access for children and newborns is compromised by faulty equipment, lack of pulse oximetry and inadequate care practices. One hospital used pulse oximetry for paediatric care. Eleven hospitals had some access to oxygen supplies. Testing of 57 oxygen concentrators revealed two (3.5%) that were ‘fit for use’. Overall, 14.4% (3708/25 677) of children and neonates received oxygen some time during their admission; 19.4% (1944/10 000) of hypoxaemic children received oxygen; 38.5% (1217/3161) of children who received oxygen therapy were not hypoxaemic.

CONCLUSIONS:
Oxygen access for children in Nigerian hospitals is poor, and likely results in substantial excess mortality. To improve oxygen access for children globally we must focus on actual provision of oxygen to patients-not simply the presence of oxygen equipment at the facility level. This requires a systematic approach to improve both oxygen (access [including equipment, maintenance and affordability]) and oxygen use (including pulse oximetry, guidelines and continuing education).

© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

KEYWORDS:
children; concentrators; hypoxaemia; newborns; oxygen therapy

PMID: 30916340 DOI: 10.1093/inthealth/ihz009
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Select item 30916178
16.
Cad Saude Publica. 2019 Mar 25;35(3):e00118118. doi: 10.1590/0102-311X00118118.
Prevalence of sexually transmitted infections and bacterial vaginosis among lesbian women: systematic review and recommendations to improve care.
Takemoto MLS1, Menezes MO1, Polido CBA2, Santos DS3, Leonello VM4, Magalhães CG5, Cirelli JF6, Knobel R7.
Author information
Abstract
Our aim was to systematically review data about the risk of sexually transmitted infections (STI) and bacterial vaginosis among lesbian women and to suggest strategies to improve prevention, diagnosis and treatment. A search strategy for lesbian, STI and bacterial vaginosis was applied to PubMed, LILACS and BDENF databases. Of 387 unique references retrieved, 22 fulfilled the inclusion criteria (cross-sectional studies reporting prevalence for 8 STIs/bacterial vaginosis and history of a STI). The most frequent infection reported was bacterial vaginosis, and none study reported data on hepatitis B. A wide range of prevalence was observed for most infections. In terms of risk factors, the number of sexual partners, the past or current smoking, a history of forced sex and sexual stigma seem to increase the risk of STI and bacterial vaginosis. The findings of this review are discussed considering guidelines directly addressing the LGBT community’s health and relevant studies investigating both safe sexual practices and the intricate relationship between LGBT people and their care providers. A set of recommendations to improve preventive care for lesbian women is proposed. Affirming that little is known about the extent of STIs and bacterial vaginosis transmission in female-to-female sexual activities or about the risk factors for STI and bacterial vaginosis among lesbian women is reasonable. In fact, the overall quality of the studies was low or very low with significant uncertainty around their findings. However, we consider that the available knowledge indicates some paths to be followed by care providers and policy decision-makers to improve their actions towards better sexual health of lesbian women.

PMID: 30916178 DOI: 10.1590/0102-311X00118118
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Select item 30916012
17.
Br J Anaesth. 2019 Feb 28. pii: S0007-0912(19)30064-9. doi: 10.1016/j.bja.2019.01.024. [Epub ahead of print]
Effectiveness of interdisciplinary interventions in paediatric chronic pain management: a systematic review and subset meta-analysis.
Liossi C1, Johnstone L2, Lilley S3, Caes L4, Williams G3, Schoth DE2.
Author information
Abstract
BACKGROUND:
Paediatric chronic pain is a significant problem that can have devastating impacts on quality of life. Multimodal interdisciplinary interventions are the mainstay of paediatric treatment. The aim of this article is to provide a comprehensive review of the effectiveness of interdisciplinary interventions in the management of paediatric chronic pain.

METHODS:
Studies were identified via a search of nine databases. The search strategy included concept blocks pertaining to type of pain, study population, and type of intervention. Eligible studies reported the effects of an intervention co-ordinated by two or more healthcare professionals of different disciplines, and recruited a sample aged 22 yr or below with chronic pain. Twenty-eight studies were included, and 21 provided data for inclusion in between- and within-groups meta-analyses.

RESULTS:
Patients randomised to interdisciplinary interventions reported significantly lower pain intensity 0-1 month post-intervention compared with patients randomised to the control groups. Within-groups analysis of patients receiving interdisciplinary interventions showed significant improvements pre- to post-intervention in pain intensity, functional disability, anxiety, depression, catastrophising, school attendance, school functioning, and pain acceptance. Few differences were found between interventions delivered in inpatient vs outpatient settings. Significant heterogeneity due mainly to differing outcome variables and intervention content was found in most analyses.

CONCLUSIONS:
Overall, interdisciplinary interventions show promise in providing a range of clinical benefits for children with chronic pain. Methodologically robust randomised controlled trials using standardised outcome measures are needed, however, to guide clinical care.

Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

KEYWORDS:
chronic pain; interdisciplinary pain clinic; meta-analysis; multimodal analgesia; paediatrics; systematic review

PMID: 30916012 DOI: 10.1016/j.bja.2019.01.024
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Select item 30916008
18.
Br J Anaesth. 2019 Mar 2. pii: S0007-0912(19)30059-5. doi: 10.1016/j.bja.2019.01.019. [Epub ahead of print]
Perioperative Quality Initiative consensus statement on postoperative blood pressure, risk and outcomes for elective surgery.
McEvoy MD1, Gupta R2, Koepke EJ3, Feldheiser A4, Michard F5, Levett D6, Thacker JKM7, Hamilton M8, Grocott MPW9, Mythen MG10, Miller TE3, Edwards MR9; POQI-3 workgroup; POQI chairs, Miller TE3, Mythen MG10, Grocott MP11, Edwards MR11; Physiology group; Preoperative blood pressure group; Intraoperative blood pressure group; Postoperative blood pressure group.
Collaborators (29)
Author information
Abstract
BACKGROUND:
Postoperative hypotension and hypertension are frequent events associated with increased risk of adverse outcomes. However, proper assessment and management is often poorly understood. As a part of the PeriOperative Quality Improvement (POQI) 3 workgroup meeting, we developed a consensus document addressing this topic. The target population includes adult, non-cardiac surgical patients in the postoperative phase outside of the ICU.

METHODS:
A modified Delphi technique was used, evaluating papers published in MEDLINE examining postoperative blood pressure monitoring, management, and outcomes. Practice recommendations were developed in line with National Institute for Health and Care Excellence guidelines.

RESULTS:
Consensus recommendations were that (i) there is evidence of harm associated with postoperative systolic arterial pressure <90 mm Hg; (ii) for patients with preoperative hypertension, the threshold at which harm occurs may be higher than a systolic arterial pressure of 90 mm Hg; (iii) there is insufficient evidence to precisely define the level of postoperative hypertension above which harm will occur; (iv) a greater frequency of postoperative blood pressure measurement is likely to identify risk of harm and clinical deterioration earlier; and (v) there is evidence of harm from withholding beta-blockers, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors in the postoperative period.

CONCLUSIONS:
Despite evidence of associations with postoperative hypotension or hypertension with worse postoperative outcome, further research is needed to define the optimal levels at which intervention is beneficial, to identify the best methods and timing of postoperative blood pressure measurement, and to refine the management of long-term antihypertensive treatment in the postoperative phase.

Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

KEYWORDS:
antihypertensive drugs; blood pressure; hypertension; hypotension; myocardial infarction; outcomes; postoperative; surgery

PMID: 30916008 DOI: 10.1016/j.bja.2019.01.019
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Select item 30916006
19.
Br J Anaesth. 2019 Mar 2. pii: S0007-0912(19)30057-1. doi: 10.1016/j.bja.2019.01.018. [Epub ahead of print]
Perioperative Quality Initiative consensus statement on preoperative blood pressure, risk and outcomes for elective surgery.
Sanders RD1, Hughes F2, Shaw A3, Thompson A4, Bader A5, Hoeft A6, Williams DA4, Grocott MPW7, Mythen MG8, Miller TE4, Edwards MR9; Perioperative Quality Initiative-3 Workgroup; POQI chairs; Physiology group; Preoperative blood pressure group; Intraoperative blood pressure group; Postoperative blood pressure group.
Collaborators (33)
Author information
Abstract
BACKGROUND:
A multidisciplinary international working subgroup of the third Perioperative Quality Initiative consensus meeting appraised the evidence on the influence of preoperative arterial blood pressure and community cardiovascular medications on perioperative risk.

METHODS:
A modified Delphi technique was used, evaluating papers published in MEDLINE on associations between preoperative numerical arterial pressure values or cardiovascular medications and perioperative outcomes. The strength of the recommendations was graded by National Institute for Health and Care Excellence guidelines.

RESULTS:
Significant heterogeneity in study design, including arterial pressure measures and perioperative outcomes, hampered the comparison of studies. Nonetheless, consensus recommendations were that (i) preoperative arterial pressure measures may be used to define targets for perioperative management; (ii) elective surgery should not be cancelled based solely upon a preoperative arterial pressure value; (iii) there is insufficient evidence to support lowering arterial pressure in the immediate preoperative period to minimise perioperative risk; and (iv) there is insufficient evidence that any one measure of arterial pressure (systolic, diastolic, mean, or pulse) is better than any other for risk prediction of adverse perioperative events.

CONCLUSIONS:
Future research should define which preoperative arterial pressure values best correlate with adverse outcomes, and whether modifying arterial pressure in the preoperative setting will change the perioperative morbidity or mortality. Additional research should define optimum strategies for continuation or discontinuation of preoperative cardiovascular medications.

Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

KEYWORDS:
arterial pressure; haemodynamics; perioperative care; preoperative blood pressure; surgical risk

PMID: 30916006 DOI: 10.1016/j.bja.2019.01.018
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Select item 30916004
20.
Br J Anaesth. 2019 Feb 27. pii: S0007-0912(19)30050-9. doi: 10.1016/j.bja.2019.01.013. [Epub ahead of print]
Perioperative Quality Initiative consensus statement on intraoperative blood pressure, risk and outcomes for elective surgery.
Sessler DI1, Bloomstone JA2, Aronson S3, Berry C4, Gan TJ5, Kellum JA6, Plumb J7, Mythen MG8, Grocott MPW9, Edwards MR7, Miller TE10; Perioperative Quality Initiative-3 workgroup; POQI chairs, Miller TE, Mythen MG, Grocott MP, Edwards MR; Physiology group; Preoperative blood pressure group; Intraoperative blood pressure group; Postoperative blood pressure group.
Collaborators (29)
Author information
Abstract
BACKGROUND:
Intraoperative mortality is now rare, but death within 30 days of surgery remains surprisingly common. Perioperative myocardial infarction is associated with a remarkably high mortality. There are strong associations between hypotension and myocardial injury, myocardial infarction, renal injury, and death. Perioperative arterial blood pressure management was thus the basis of a Perioperative Quality Initiative consensus-building conference held in London in July 2017.

METHODS:
The meeting featured a modified Delphi process in which groups addressed various aspects of perioperative arterial pressure.

RESULTS:
Three consensus statements on intraoperative blood pressure were established. 1) Intraoperative mean arterial pressures below 60-70 mm Hg are associated with myocardial injury, acute kidney injury, and death. Injury is a function of hypotension severity and duration. 2) For adult non-cardiac surgical patients, there is insufficient evidence to recommend a general upper limit of arterial pressure at which therapy should be initiated, although pressures above 160 mm Hg have been associated with myocardial injury and infarction. 3) During cardiac surgery, intraoperative systolic arterial pressure above 140 mm Hg is associated with increased 30 day mortality. Injury is a function of arterial pressure severity and duration.

CONCLUSIONS:
There is increasing evidence that even brief durations of systolic arterial pressure <100 mm Hg and mean arterial pressure <60-70 mm Hg are harmful during non-cardiac surgery.

Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

KEYWORDS:
anaesthesia; arterial pressure; hypotension; mortality; myocardial injury; postoperative outcome; renal injury; surgery

PMID: 30916004 DOI: 10.1016/j.bja.2019.01.013
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