Intravenous fluid therapy: an audit and discussion of improvements required for prescribers and administrators.

BACKGROUND: Foundation doctors and nurses are the clinicians most closely involved in fluid assessment, intravenous (IV) fluid prescription and administration. However, both groups report challenges regarding IV fluids. At a large NHS trust in England, adherence to the National Institute for Health and Care Excellence (NICE) guideline CG174, regarding IV fluids, was largely unknown. AIMS: To assess the baseline adherence, within the hospitals, to CG174 and identify areas for improvement. METHODS: A set of 12 audit standards were developed and used to collect data across 29 clinical areas between September 2022 and May 2023, with 255 patients receiving IV fluids at any time during their inpatient stay included. FINDINGS: For two standards target adherence of 95% was achieved, with an adherence less than 50% in most. Areas of particularly poor adherence included assessing and meeting fluid and electrolyte requirements, patient reassessment and developing IV fluid management plans. CONCLUSION: Trust baseline adherence to NICE CG174 requires improvement, particularly regarding patient assessment and reassessment, and meeting electrolyte requirements.

Prevalence of moderate or greater permanent childhood hearing impairment and effectiveness of targeted surveillance for babies who pass newborn hearing screening.

OBJECTIVE: To assess the utility of targeted surveillance for the identification of moderate to profound PCHI in babies who pass newborn hearing screening in England and have risk factors. DESIGN: Retrospective analysis. STUDY SAMPLE: A total of 3,957,891 children born 01/04/2012-31/03/2018 in England. RESULTS: A total of 7148 PCHI cases were identified (1.81 per 1,000 babies). 6,707 followed an immediate referral from the screen (1 per 16 referrals), 51 followed targeted surveillance referral (1 per 540 referrals) and 390 without a referral. Audiology uptake was higher following an immediate referral (96.7% overall, 77.2% within NHSP-defined timescales) than following targeted surveillance (63.8% overall, 51.1% within 52 weeks of birth). The screening was 94.5% sensitive overall, with similar sensitivities for each of the risk factors. General linearised logistic regression models identified syndrome as the risk factor with the highest odds ratio (14.08 for all babies, 22.19 for babies without immediate referral). Close family history of hearing loss was the next highest (10.93 for all babies, 12.29 for babies without immediate referral). CONCLUSION: The evidence for a targeted surveillance programme, based on risk factors, for babies in England who pass the newborn screen is not strong.

Improving outcome of sepsis on the ward: introducing the 'Sepsis Six' bundle.

BACKGROUND: The Sepsis Six bundle is designed to facilitate early intervention with three diagnostic and three therapeutic steps to be delivered within 1 h to patients with suspected sepsis. AIMS AND OBJECTIVES: To investigate the effects of delivering the 'Sepsis Six' bundle by the Critical Care Outreach team on patient outcomes. DESIGN: In a prospective observational study, all adult patients on the general wards from June 2012 to January 2014 with sepsis who were screened and treated by the Critical Care Outreach team were included. METHODS: The main outcome measure was the change in National Early Warning Score following the delivery of the Sepsis Six bundle within 24 h. Secondary outcomes were 90-day mortality and overall bundle compliance. RESULTS: A total of 207 patients were included in the analysis. Overall bundle compliance was 84%. National Early Warning Scores decreased significantly 24 h after administering the Sepsis Six, from 7·4 ± 2·6 to 3·1 ± 2·4 (p < 0·001). The distribution of the National Early Warning Score changed significantly. Mortality was lower at 90 days when patients who presented with signs of sepsis within 48 h of hospital admission were compared with those who presented with signs of sepsis after 48 h of hospital admission (14·5% versus 35·4% p < 0·03) despite similar baseline physiological variables. CONCLUSIONS: We found better outcomes after the administration of Sepsis Six. Reliable delivery of the bundle, defined as 80% of patients receiving the standard of care, is achievable, and our quality improvement data suggest that it is likely to be sustainable in our environment. RELEVANCE TO CLINICAL PRACTICE: Sepsis Six can reduce physiological impairment, monitored by the National Early Warning Scores. Consistent delivery of the bundle can lead to better patient outcomes.

Measurement of blood pressure for the diagnosis and management of hypertension in different ethnic groups: one size fits all.

BACKGROUND: Hypertension is a major risk factor for cardiovascular disease and prevalence varies by ethnic group. The diagnosis and management of blood pressure are informed by guidelines largely based on data from white populations. This study addressed whether accuracy of blood pressure measurement in terms of diagnosis of hypertension varies by ethnicity by comparing two measurement modalities (clinic blood pressure and home monitoring) with a reference standard of ambulatory BP monitoring in three ethnic groups. METHODS: Cross-sectional population study (June 2010 - December 2012) with patients (40-75 years) of white British, South Asian and African Caribbean background with and without a previous diagnosis of hypertension recruited from 28 primary care practices. The study compared the test performance of clinic BP (using various protocols) and home-monitoring (1 week) with a reference standard of mean daytime ambulatory measurements using a threshold of 140/90 mmHg for clinic and 135/85 mmHg for out of office measurement. RESULTS: A total of 551 participants had complete data of whom 246 were white British, 147 South Asian and 158 African Caribbean. No consistent difference in accuracy of methods of blood pressure measurement was observed between ethnic groups with or without a prior diagnosis of hypertension: for people without hypertension, clinic measurement using three different methodologies had high specificity (75-97%) but variable sensitivity (33-65%) whereas home monitoring had sensitivity of 68-88% and specificity of 64-80%. For people with hypertension, detection of a raised blood pressure using clinic measurements had sensitivities of 34-69% with specificity of 73-92% and home monitoring had sensitivity (81-88%) and specificity (55-65%). CONCLUSIONS: For people without hypertension, ABPM remains the choice for diagnosing hypertension compared to the other modes of BP measurement regardless of ethnicity. Differences in accuracy of home monitoring and clinic monitoring (higher sensitivity of the former; higher specificity of the latter) were also not affected by ethnicity.

Performance and characteristics of the Newborn Hearing Screening Programme in England: The first seven years.

OBJECTIVE: To assess the performance of the universal newborn hearing screen in England. DESIGN: Retrospective analysis of population screening records. STUDY SAMPLE: A total of 4 645 823 children born 1 April 2004 to 31 March 2013. RESULTS: 97.5% of the eligible population complete screening by 4/5 weeks of age and 98.9% complete screening by three months of age. The refer rate for the 12/13 birth cohort is 2.6%. The percentage of screen positive (i.e. referred) babies commencing follow up by four weeks of age and six months of age is 82.5% and 95.8% respectively. The yield of bilateral PCHL from the screen is around 1/1000. For bilateral PCHL in the 12/13 birth cohort the median age is nine days at screen completion, 30 days at entry into follow up, 49 days at confirmation, 50 days at referral to early intervention, and 82 days at hearing-aid fitting. CONCLUSION: The performance of the newborn hearing screening programme has improved continuously. The yield of bilateral PCHL from the screen is about 1/1000 as expected. The age of identification and management is well within the first six months of life, although there remains scope for further improvement with respect to timely entry into follow up.

Comparing the monitoring of patients transferred from a critical care unit to hospital wards at after-hours with day transfers: an exploratory, prospective cohort study.

AIMS: To investigate possible factors related to patient monitoring to explain the higher mortality rates associated with after-hours transfers compared with daytime transfers from critical care units to the wards. BACKGROUND: International research suggests that patients transferred from critical care units after-hours have a higher mortality rate than transfers during daytime, although the reasons remain unknown. DESIGN: A prospective exploratory study. METHODS: Twenty-nine patients transferred from a UK critical care unit to a ward within the same hospital after-hours for 10 weeks beginning April 2009 were compared with 29 transfers during daytime hours matched on potentially confounding characteristics. UK Critical Care Unit transfer guidelines have remained unchanged since data collection. Outcomes were as follows: (i) frequency of nursing observations; (ii) time periods from transfer to first medical review; (iii) time period from transfer to first clinical observations; (iv) frequency of transfer to an inappropriate ward; (v) delayed transfers from Critical Care Unit to ward. RESULTS: Using Wilcoxon's Rank test (two tail) to compare paired data from the matched groups, observations were recorded significantly less frequently within the first 12 hours for after-hours transfers. Time from transfer to first clinical observations was significantly longer for after-hour transfer patients. The delay from when the patient was ready for ward care and actual transfer was also longer for the after-hours transfer group. CONCLUSIONS: Surveillance differences, including time to the first set of observations and frequency of observations in the first 12 hours, are potential factors that may explain the differential mortality associated with after-hours transfers.

Behavioral counseling after screening for alcohol misuse in primary care: a systematic review and meta-analysis for the U.S. Preventive Services Task Force.

BACKGROUND: Alcohol misuse, which includes the full spectrum from risky drinking to alcohol dependence, is a leading cause of preventable death in the United States. PURPOSE: To evaluate the benefits and harms of behavioral counseling interventions for adolescents and adults who misuse alcohol. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Library, CINAHL, PsycINFO, International Pharmaceutical Abstracts, and reference lists of published literature (January 1985 through January 2012, limited to English-language articles). STUDY SELECTION: Controlled trials at least 6 months' duration that enrolled persons with alcohol misuse identified by screening in primary care settings and evaluated behavioral counseling interventions. DATA EXTRACTION: One reviewer extracted data and a second checked accuracy. Two independent reviewers assigned quality ratings and graded the strength of the evidence. DATA SYNTHESIS: The 23 included trials generally excluded persons with alcohol dependence. The best evidence was for brief (10- to 15-minute) multicontact interventions. Among adults receiving behavioral interventions, consumption decreased by 3.6 drinks per week from baseline (weighted mean difference, 3.6 drinks/wk [95% CI, 2.4 to 4.8 drinks/wk]; 10 trials; 4332 participants), 12% fewer adults reported heavy drinking episodes (risk difference, 0.12 [CI, 0.07 to 0.16]; 7 trials; 2737 participants), and 11% more adults reported drinking less than the recommended limits (risk difference, 0.11 [CI, 0.08 to 0.13]; 9 trials; 5973 participants) over 12 months compared with control participants (moderate strength of evidence). Evidence was insufficient to draw conclusions about accidents, injuries, or alcohol-related liver problems. Trials enrolling young adults or college students showed reduced consumption and fewer heavy drinking episodes (moderate strength of evidence). Little or no evidence of harms was found. LIMITATIONS: Results may be biased to the null because the behavior of control participants could have been affected by alcohol misuse assessments. In addition, evidence is probably inapplicable to persons with alcohol dependence and selective reporting may have occurred. CONCLUSION: Behavioral counseling interventions improve behavioral outcomes for adults with risky drinking. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Effectiveness of targeted surveillance to identify moderate to profound permanent childhood hearing impairment in babies with risk factors who pass newborn screening.

OBJECTIVE: To examine the effectiveness of targeted surveillance for the identification of moderate-profound PCHI in babies who pass the newborn hearing screen in England and have risk factors. DESIGN: Retrospective analysis. STUDY SAMPLE: 2,307,880 children born 01/04/06-30/09/09 in England. RESULTS: Overall the prevalence for all PCHI in children with risk factors who pass newborn hearing screening is 1.49/1000. The risk factors with the highest prevalence are (1) Syndrome (other than Down's) associated with a hearing loss; (2) NICU with refer in both ears at OAE and pass in both ears at AABR; (3) Craniofacial anomaly; (4) Down's syndrome; (5) Congenital infection. CONCLUSION: Targeted surveillance for children who pass the screen and have the risk factors 1-5 listed above will be retained within the English NHSP; targeted surveillance for children who pass the screen and have other risk factors is not effective and has been discontinued.

ABPM is best for diagnosing hypertension in primary care.

Ambulatory blood pressure monitoring (ABPM) is more accurate than clinic and home monitoring in diagnosing hypertension. A diagnostic strategy for hypertension using ABPM following an initial raised clinic reading would reduce misdiagnosis and NHS costs. If the first and second measurements taken during a consultation are both > or = 140/90 mmHg, 24-hour ABPM should be used to confirm the diagnosis of hypertension. Home monitoring can be used to confirm the diagnosis if the patient cannot tolerate ABPM. In cases of severe hypertension (clinic BP > or = 180/110 mmHg) and evidence of target organ damage, antihypertensive drug treatment should be started immediately without waiting for the results of ABPM or home monitoring. ABPM estimates true mean BP more accurately than clinic measurement because multiple readings are taken. It has been shown to have better correlation with a range of cardiovascular outcomes and end organ damage, Out-of-office methods can enable a diagnosis to be made more quickly. The benefits of these techniques, in particular ABPM, include the correct diagnosis of white coat hypertension and improved diagnostic accuracy. The weight of evidence suggests ABPM is the best prognostic indicator, followed by home then clinic monitoring. Stage 1 patients should only be offered antihypertensives if they have increased cardiovascular risk due to concurrent diabetes, chronic kidney disease, established CVD, target organ damage or a 10-year CVD risk >20%. Stage 2 patients should all be offered antihypertensives following ABPM or home monitoring, irrespective of their background cardiovascular risk.

Empirical study of unipolar and bipolar configurations using high resolution single multi-walled carbon nanotube electrodes for electrophysiological probing of electrically excitable cells.

Identifying the neurophysiological basis underlying learning and memory in the mammalian central nervous system requires the development of biocompatible, high resolution, low electrode impedance electrophysiological probes; however, physically, electrode impedance will always be finite and, at times, large. Herein, we demonstrate through experiments performed on frog sartorius muscle that single multi-walled carbon nanotube electrode (sMWNT electrode) geometry and placement are two degrees of freedom that can improve biocompatibility of the probe and counteract the detrimental effects of MWNT/electrolyte interface impedance on the stimulation efficiency and signal-to-noise ratio (SNR). We show that high aspect ratio dependent electric field enhancement at the MWNT tip can boost stimulation efficiency. Derivation of the sMWNT electrode's electrical equivalent indicates that, at low stimulus voltage regimes below 1 V, current conduction is mediated by charge fluctuation in the double layer obviating electrolysis of water, which is potentially toxic to pH sensitive biological tissue. Despite the accompanying increase in electrode impedance, a pair of closely spaced sMWNT electrodes in a two probe (bipolar) configuration maintains biocompatibility and enhances stimulation efficiency and SNR compared to the single probe (unipolar) configuration. For stimulus voltages below 1 V, the electrical equivalent verifies that current conduction in the two probe configuration still proceeds via charge fluctuation in the double layer. As an extracellular stimulation electrode, the two sMWNT electrodes comprise a current dipole that concentrates the electric field and the current density in a smaller region of sartorius; consequently, the bipolar configuration can elicit muscle fiber twitching at low voltages that preclude electrolysis of water. When recording field potentials, the bipolar configuration subtracts the potential between two points allowing for the detection of higher signal amplitudes. As a result, SNR is improved. These results indicate that use of the high aspect ratio MWNT in a bipolar configuration can achieve a biocompatible electrode that offers enhanced stimulation efficiency and higher SNR.

The Impact of an Electronic Patient Bedside Observation and Handover System on Clinical Practice: Mixed-Methods Evaluation.

BACKGROUND: Patient safety literature has long reported the need for early recognition of deteriorating patients. Early warning scores (EWSs) are commonly implemented as "track and trigger," or rapid response systems for monitoring and early recognition of acute patient deterioration. This study presents a human factors evaluation of a hospital-wide transformation in practice, engendered by the deployment of an innovative electronic observations (eObs) and handover system. This technology enables real-time information processing at the patient's bedside, improves visibility of patient data, and streamlines communication within clinical teams. OBJECTIVE: The aim of this study was to identify improvement and deterioration in workplace efficiency and quality of care resulting from the large-scale imposition of new technology. METHODS: A total of 85 hours of direct structured observations of clinical staff were carried out before and after deployment. We conducted 40 interviews with a range of clinicians. A longitudinal analysis of critical care audit and electronically recorded patient safety incident reports was conducted. The study was undertaken in a large secondary-care facility in the United Kingdom. RESULTS: Roll-out of eObs was associated with approximately 10% reduction in total unplanned admissions to critical care units from eObs-equipped wards. Over time, staff appropriated the technology as a tool for communication, workload management, and improving awareness of team capacity. A negative factor was perceived as lack of engagement with the system by senior clinicians. Doctors spent less time in the office (68.7% to 25.6%). More time was spent at the nurses' station (6.6% to 41.7%). Patient contact time was more than doubled (2.9% to 7.3%). CONCLUSIONS: Since deployment, clinicians have more time for patient care because of reduced time spent inputting and accessing data. The formation of a specialist clinical team to lead the roll-out was universally lauded as the reason for success. Staff valued the technology as a tool for managing workload and identified improved situational awareness as a key benefit. For future technology deployments, the staff requested more training preroll-out, in addition to engagement and support from senior clinicians.

Predicting 30-day mortality in patients with sepsis: An exploratory analysis of process of care and patient characteristics.

BACKGROUND: Sepsis represents a significant public health burden, costing the NHS £2.5 billion annually, with 35% mortality in 2006. The aim of this exploratory study was to investigate risk factors predictive of 30-day mortality amongst patients with sepsis in Nottingham. METHODS: Data were collected prospectively from adult patients with sepsis in Nottingham University Hospitals NHS Trust as part of an on-going quality improvement project between November 2011 and March 2014. Patients admitted to critical care with the diagnosis of sepsis were included in the study. In all, 97 separate variables were investigated for their association with 30-day mortality. Variables included patient demographics, symptoms of systemic inflammatory response syndrome, organ dysfunction or tissue hypoperfusion, locations of early care, source of sepsis and time to interventions. RESULTS: A total of 455 patients were included in the study. Increased age (adjOR = 1.05 95%CI = 1.03-1.07 p < 0.001), thrombocytopenia (adjOR = 3.10 95%CI = 1.23-7.82 p = 0.016), hospital-acquired sepsis (adjOR = 3.34 95%CI = 1.78-6.27 p < 0.001), increased lactate concentration (adjOR = 1.16 95%CI = 1.06-1.27 p = 0.001), remaining hypotensive after vasopressors (adjOR = 3.89 95%CI = 1.26-11.95 p = 0.02) and mottling (adjOR = 3.80 95%CI = 1.06-13.55 p = 0.04) increased 30-day mortality odds. Conversely, fever (adjOR = 0.46 95%CI = 0.28-0.75 p = 0.002), fluid refractory hypotension (adjOR = 0.29 95%CI = 0.10-0.87 p = 0.027) and being diagnosed in surgical wards (adjOR = 0.35 95%CI = 0.15-0.81 p = 0.015) were protective. Treatment timeliness were not significant factors. CONCLUSION: Several important predictors of 30-day mortality were found by this research. Retrospective analysis of our sepsis data has revealed mortality predictors that appear to be more patient-related than intervention-specific. With this information, care can be improved for those identified most at risk of death.

Cancer suspicion in general practice, urgent referral, and time to diagnosis: a population-based GP survey nested within a feasibility study using information technology to flag-up patients with symptoms of colorectal cancer.

BACKGROUND: Patients with symptoms of possible colorectal cancer are not always referred for investigation. AIM: To ascertain barriers and facilitators to GP referral of patients meeting the National Institute for Health and Care Excellence (NICE) guidelines for urgent referral for suspected colorectal cancer. DESIGN & SETTING: Qualitative study in the context of a feasibility study using information technology in GP practices to flag-up patients meeting urgent referral criteria for colorectal cancer. METHOD: Semi-structured interview with 18 GPs and 12 practice managers, focusing on early detection of colorectal cancer, issues in the use of information technology to identify patients and GP referral of these patients for further investigation were audiotaped, transcribed verbatim, and analysed according to emergent themes. RESULTS: There were two main themes: wide variation in willingness to refer and uncertainty about whether to refer; and barriers to referral. Three key messages emerged: there was a desire to avoid over-referral, lack of knowledge of guidelines, and the use of individually-derived decision rules for further investigation or referral of symptoms. Some GPs were unaware that iron deficiency anaemia or persistent diarrhoea are urgent referral criteria. Alternatives to urgent referral included undertaking no investigations, trials of iron therapy, use of faecal occult blood tests (FOBt) and non-urgent referral. In minority ethnic groups (South Asians) anaemia was often accepted as normal.Concerns about over-referral were linked to financial pressures and perceived criticism by healthcare commissioners, and a reluctance to scare patients by discussing suspected cancer. CONCLUSION: GPs' lack of awareness of referral guidelines and concerns about over-referral are barriers to early diagnosis of colorectal cancer.

The Herts and minds study: evaluating the effectiveness of mentalization-based treatment (MBT) as an intervention for children in foster care with emotional and/or behavioural problems: a phase II, feasibility, randomised controlled trial.

BACKGROUND: A significant proportion of children in the social care system in England present with mental health problems, with the majority experiencing some form of emotional and behavioural difficulties. The most effective treatments for these children are currently unknown, partly due to a lack of robust, controlled studies. Researchers have identified a number of obstacles to conducting well-designed research with this population, making the need to test the feasibility of a randomised controlled trial especially important. METHODS/DESIGN: This protocol outlines a two-arm, randomised control feasibility trial to explore the acceptability and credibility of mentalization-based treatment (MBT) as a treatment for reducing emotional and behavioural difficulties in looked after children and to test the possibility of addressing a number of methodological challenges to conducting high-quality research with this population. MBT is a relatively new intervention which, in the adaptation of the model tested here, includes many of the features of therapy identified in NICE guidelines as necessary to support children in care. The two arms are MBT and usual clinical care (UCC). The study will take place in Hertfordshire Partnership University NHS Foundation Trust with follow-up at 12 and 24 weeks. DISCUSSION: This study will aim to ascertain whether it is worthwhile and feasible to progress to testing the intervention in a full-scale definitive randomised controlled trial (RCT). This study therefore has the potential to improve our understanding of the obstacles to conducting high-quality research with this very vulnerable population, and in the medium term, could help to improve the stability of foster placements and the emotional well-being of children in care. TRIAL REGISTRATION: ISRCTN90349442.

Interarm Difference in Systolic Blood Pressure in Different Ethnic Groups and Relationship to the "White Coat Effect": A Cross-Sectional Study.

BACKGROUND: Interarm differences (IADs) ≥10 mm Hg in systolic blood pressure (BP) are associated with greater incidence of cardiovascular disease. The effect of ethnicity and the white coat effect (WCE) on significant systolic IADs (ssIADs) are not well understood. METHODS: Differences in BP by ethnicity for different methods of BP measurement were examined in 770 people (300 White British, 241 South Asian, 229 African-Caribbean). Repeated clinic measurements were obtained simultaneously in the right and left arm using 2 BPTru monitors and comparisons made between the first reading, mean of second and third and mean of second to sixth readings for patients with, and without known hypertension. All patients had ambulatory BP monitoring (ABPM). WCE was defined as systolic clinic BP ≥10 mm Hg higher than daytime ABPM. RESULTS: No significant differences were seen in the prevalence of ssIAD between ethnicities whichever combinations of BP measurement were used and regardless of hypertensive status. ssIADs fell between the 1st measurement (161, 22%), 2nd/3rd (113, 16%), and 2nd-6th (78, 11%) (1st vs. 2nd/3rd and 2nd-6th, P < 0.001). Hypertensives with a WCE were more likely to have ssIADs on 1st, (odds ratio [OR] 1.73 (95% confidence interval 1.04-2.86); 2nd/3rd, (OR 3.05 (1.68-5.53); and 2nd-6th measurements, (OR 2.58 (1.22-5.44). Nonhypertensive participants with a WCE were more likely to have a ssIAD on their first measurement (OR 3.82 (1.77 to -8.25) only. CONCLUSIONS: ssIAD prevalence does not vary with ethnicity regardless of hypertensive status but is affected by the number of readings, suggesting the influence of WCE. Multiple readings should be used to confirm ssIADs.

The transition into adoptive parenthood: Adoption as a process of continued unsafe uncertainty when family scripts collide.

Our prospective study investigated couples' expectations of adoptive parenthood and explored how these changed with their actual experience of parenthood. Six heterosexual couples were interviewed just before placement began and 6 months after the children had arrived. Interpretative Phenomenological Analysis (IPA) was used to analyse both sets of interview data. Expectations of adoptive parenthood mostly transformed smoothly into adoption experience for couples, but challenges were experienced when family scripts collided and a continued feeling of unsafe uncertainty then prevailed within these newly formed family systems. Family script collision seemed a particular problem for couples adopting sibling pairs. To further professional practice in working with families over the transition to adoptive parenting, we suggest that professionals keep in mind a framework that includes the following: Internal and external world influences on family members, Intergenerational issues, Family scripts and the Structural challenges of adoption (IIFS).

Blood pressure variability and cardiovascular disease: systematic review and meta-analysis.

OBJECTIVE:  To systematically review studies quantifying the associations of long term (clinic), mid-term (home), and short term (ambulatory) variability in blood pressure, independent of mean blood pressure, with cardiovascular disease events and mortality. DATA SOURCES:  Medline, Embase, Cinahl, and Web of Science, searched to 15 February 2016 for full text articles in English. ELIGIBILITY CRITERIA FOR STUDY SELECTION:  Prospective cohort studies or clinical trials in adults, except those in patients receiving haemodialysis, where the condition may directly impact blood pressure variability. Standardised hazard ratios were extracted and, if there was little risk of confounding, combined using random effects meta-analysis in main analyses. Outcomes included all cause and cardiovascular disease mortality and cardiovascular disease events. Measures of variability included standard deviation, coefficient of variation, variation independent of mean, and average real variability, but not night dipping or day-night variation. RESULTS:  41 papers representing 19 observational cohort studies and 17 clinical trial cohorts, comprising 46 separate analyses were identified. Long term variability in blood pressure was studied in 24 papers, mid-term in four, and short-term in 15 (two studied both long term and short term variability). Results from 23 analyses were excluded from main analyses owing to high risks of confounding. Increased long term variability in systolic blood pressure was associated with risk of all cause mortality (hazard ratio 1.15, 95% confidence interval 1.09 to 1.22), cardiovascular disease mortality (1.18, 1.09 to 1.28), cardiovascular disease events (1.18, 1.07 to 1.30), coronary heart disease (1.10, 1.04 to 1.16), and stroke (1.15, 1.04 to 1.27). Increased mid-term and short term variability in daytime systolic blood pressure were also associated with all cause mortality (1.15, 1.06 to 1.26 and 1.10, 1.04 to 1.16, respectively). CONCLUSIONS:  Long term variability in blood pressure is associated with cardiovascular and mortality outcomes, over and above the effect of mean blood pressure. Associations are similar in magnitude to those of cholesterol measures with cardiovascular disease. Limited data for mid-term and short term variability showed similar associations. Future work should focus on the clinical implications of assessment of variability in blood pressure and avoid the common confounding pitfalls observed to date. SYSTEMATIC REVIEW REGISTRATION:  PROSPERO CRD42014015695.