Initial Reduction in Ulcer Size As a Prognostic Indicator for Complete Wound Healing: A Systematic Review of Diabetic Foot and Venous Leg Ulcers.

Significance: Percent area reduction (PAR) is commonly reported in trials including diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs). It is unclear how well PAR performs as a surrogate marker for complete wound closure. This review aimed to summarize all available evidence evaluating PAR as a predictor of complete DFU and VLU healing. Recent Advances: A review searching the CENTRAL, MEDLINE, EMBASE, and EMCARE databases was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Randomized-controlled trials and observational studies reporting PAR and any measure of its predictive ability were included. Outcomes included performance measures of PAR, timing of PAR, outcome measurement, and specific PAR cutoffs. Critical Issues: Meta-analysis was not possible due to high variability in wound duration at study start (2-48 weeks), PAR timing (2-8 weeks), PAR cutoff (-3% to 90%; determined post hoc in most studies), and outcome assessment (10-24 weeks). Six studies (21,430 DFU patients) report PAR as having acceptable to outstanding discriminatory ability (C-statistic 0.720-0.910). Five studies (29,775 VLU patients) report PAR as having poor to excellent discriminatory ability (C-statistic 0.680-0.830). One study (241 DFU and VLU patients) reports PAR sensitivity and specificity of 58.5% and 90.5%, respectively. All studies were determined to have high risk of bias. Future Directions: Despite promising discriminatory ability, most studies report post hoc analysis of patients in randomized trials, are highly heterogenous in study design, and have high risk of bias. There is scant evidence to support PAR in isolation as a surrogate for complete DFU or VLU healing in routine clinical practice.

Associations with Post-Consultation Health-Status in Primary Care Managed Acute Exacerbation of COPD.

BACKGROUND: It has been demonstrated that antibiotic prescribing for Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) can be safely reduced in primary care when general practitioners have access to C-reactive protein (CRP) rapid testing. AIM: To investigate the factors associated with post-consultation COPD health status in patients presenting with AECOPD in this setting. DESIGN AND SETTING: A cohort study of patients enrolled in a randomised controlled trial. Patients aged 40+ years with a clinical diagnosis of COPD who presented in primary care across England and Wales with an AECOPD were included. METHODS: Participants were contacted for follow-up at one- and two-weeks by phone and attended the practice four weeks after the index consultation. The outcome of interest was the Clinical COPD Questionnaire (CCQ) score. Multivariable multilevel linear regression models fitted to examine the factors associated with COPD health status in the four-weeks following consultation for an AECOPD. RESULTS: A total of 649 patients were included, with 1947 CCQ total scores analysed. Post-consultation CCQ total scores were significantly higher (worse) in participants with diabetes (adjusted mean difference [AMD]=0.26; 95% confidence interval (CI) 0.08-0.45), obese patients compared to those with normal body mass index (AMD = 0.25, 95% CI 0.07-0.43), and those who were prescribed oral antibiotics in the prior 12 months (AMD = 0.26; 95% CI 0.11-0.41), but only the two latter associations remained after adjusting for other sociodemographic variables. CONCLUSION: COPD health status was worse in the four weeks following primary care consultation for AECOPD in patients with obesity and those prescribed oral antibiotics in the preceding year.

Associations with antibiotic prescribing for acute exacerbation of COPD in primary care: secondary analysis of a randomised controlled trial.

BACKGROUND: C-reactive protein (CRP) point-of-care testing can reduce antibiotic use in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in primary care, without compromising patient care. Further safe reductions may be possible. AIM: To investigate the associations between presenting features and antibiotic prescribing in patients with AECOPD in primary care. DESIGN AND SETTING: Secondary analysis of a randomised controlled trial of participants presenting with AECOPD in primary care (the PACE trial). METHOD: Clinicians collected participants' demographic features, comorbid illnesses, clinical signs, and symptoms. Antibiotic prescribing decisions were made after participants were randomised to receive a point-of-care CRP measurement or usual care. Multivariable regression models were fitted to explore the association between patient and clinical features and antibiotic prescribing, and extended to further explore any interactions with CRP measurement category (CRP not measured, CRP <20 mg/l, or CRP ≥20 mg/l). RESULTS: A total of 649 participants from 86 general practices across England and Wales were included. Odds of antibiotic prescribing were higher in the presence of clinician-recorded crackles (adjusted odds ratio [AOR] = 5.22, 95% confidence interval [CI] = 3.24 to 8.41), wheeze (AOR = 1.64, 95% CI = 1.07 to 2.52), diminished vesicular breathing (AOR = 2.95, 95% CI = 1.70 to 5.10), or clinician-reported evidence of consolidation (AOR = 34.40, 95% CI = 2.84 to 417.27). Increased age was associated with lower odds of antibiotic prescribing (AOR per additional year increase = 0.98, 95% CI = 0.95 to 1.00), as was the presence of heart failure (AOR = 0.32, 95% CI = 0.12 to 0.85). CONCLUSION: Several demographic features and clinical signs and symptoms are associated with antibiotic prescribing in AECOPD. Diagnostic and prognostic value of these features may help identify further safe reductions.

Cost of managing patients with venous leg ulcers.

The aim of this study was to estimate costs associated with the management of patients with venous leg ulcers (VLUs) from the perspective of the UK National Health Service (NHS). The analysis was undertaken through the Secure Anonymised Information Linkage Databank which brings together and anonymously links a wide range of person-based data from around 75% of general practitioner (GP) practices within Wales (population coverage ~2.5 million). The data covered an 11-year period from 2007 to 2017. All patients linked to the relevant codes were tracked through primary care settings, recording the number of GP practice visits (number of days with an event recorded), and wound treatment utilisation (eg, dressings, bandages, etc.) Resources were valued in monetary terms (£ sterling) and the costs were determined from national published sources of unit costs. This is the first attempt to estimate the costs of managing of VLUs using routine data sources. The direct costs to the Welsh NHS are considerable and represent 1.2% of the annual budget. Nurse visits are the main cost driver with annual estimates of £67.8 million. At a UK level, these costs amount to £1.98 billion. Dressings and compression bandages are also major cost drivers with annual Welsh estimates of £828 790. The direct cost of managing patients with VLUs is £7706 per patient per annum, which translates to an annual cost of over £2 billion, when extrapolated to the UK population. The primary cost driver is the number of district nurse visits. Initiatives to reduce healing times through improving accuracy of initial diagnosis, and improved evidence-based treatment pathways would result in major financial savings.

C-reactive protein point-of-care testing for safely reducing antibiotics for acute exacerbations of chronic obstructive pulmonary disease: the PACE RCT.

BACKGROUND: Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed antibiotics, but these may not be beneficial, and they can cause side effects and increase the risk of subsequent resistant infections. Point-of-care tests (POCTs) could safely reduce inappropriate antibiotic prescribing and antimicrobial resistance. OBJECTIVE: To determine whether or not the use of a C-reactive protein (CRP) POCT to guide prescribing decisions for AECOPD reduces antibiotic consumption without having a negative impact on chronic obstructive pulmonary disease (COPD) health status and is cost-effective. DESIGN: A multicentre, parallel-arm, randomised controlled open trial with an embedded process, and a health economic evaluation. SETTING: General practices in Wales and England. A UK NHS perspective was used for the economic analysis. PARTICIPANTS: Adults (aged ≥ 40 years) with a primary care diagnosis of COPD, presenting with an AECOPD (with at least one of increased dyspnoea, increased sputum volume and increased sputum purulence) of between 24 hours' and 21 days' duration. INTERVENTION: CRP POCTs to guide antibiotic prescribing decisions for AECOPD, compared with usual care (no CRP POCT), using remote online randomisation. MAIN OUTCOME MEASURES: Patient-reported antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status as measured with the Clinical COPD Questionnaire (CCQ) at 2 weeks. For the economic evaluation, patient-reported resource use and the EuroQol-5 Dimensions were included. RESULTS: In total, 653 participants were randomised from 86 general practices. Three withdrew consent and one was randomised in error, leaving 324 participants in the usual-care arm and 325 participants in the CRP POCT arm. Antibiotics were consumed for AECOPD by 212 out of 274 participants (77.4%) and 150 out of 263 participants (57.0%) in the usual-care and CRP POCT arm, respectively [adjusted odds ratio 0.31, 95% confidence interval (CI) 0.20 to 0.47]. The CCQ analysis comprised 282 and 281 participants in the usual-care and CRP POCT arms, respectively, and the adjusted mean CCQ score difference at 2 weeks was 0.19 points (two-sided 90% CI -0.33 to -0.05 points). The upper limit of the CI did not contain the prespecified non-inferiority margin of 0.3. The total cost from a NHS perspective at 4 weeks was £17.59 per patient higher in the CRP POCT arm (95% CI -£34.80 to £69.98; p = 0.408). The mean incremental cost-effectiveness ratios were £222 per 1% reduction in antibiotic consumption compared with usual care at 4 weeks and £15,251 per quality-adjusted life-year gained at 6 months with no significant changes in sensitivity analyses. Patients and clinicians were generally supportive of including CRP POCT in the assessment of AECOPD. CONCLUSIONS: A CRP POCT diagnostic strategy achieved meaningful reductions in patient-reported antibiotic consumption without impairing COPD health status or increasing costs. There were no associated harms and both patients and clinicians valued the diagnostic strategy. FUTURE WORK: Implementation studies that also build on our qualitative findings could help determine the effect of this intervention over the longer term. TRIAL REGISTRATION: Current Controlled Trials ISRCTN24346473. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 15. See the NIHR Journals Library website for further project information.

People with chronic obstructive pulmonary disease (COPD) often experience flare-ups known as acute exacerbations of chronic obstructive pulmonary disease. Antibiotics are prescribed for most flare-ups, but they do not always benefit patients and may cause harm, such as side effects or subsequent infections that are resistant. Rapid point-of-care tests (POCTs) can be used to help determine when antibiotics are more likely to be needed. C-reactive protein (CRP) is a marker of inflammation that can be measured with a POCT. Patients with flare-ups and a low CRP value are less likely to benefit from antibiotics. The PACE trial asked whether or not measuring CRP with a POCT could lead to fewer antibiotics being consumed for flare-ups, without having negative effects for patients. We aimed to recruit 650 patients with a COPD flare-up from primary care. Patients were randomly assigned to either (1) usual care with the addition of a CRP POCT, or (2) usual care without the addition of the test. Antibiotic use over the first 4 weeks and patients' self-assessment of their health 2 weeks after enrolment were measured in both groups. Patients in the CRP test group used fewer antibiotics than those managed as usual, and had improved patient-reported outcomes. Costs were a little higher in the CRP POCT group. Interviews with patients and clinicians found that they appreciated the CRP test being included in the decision-making process.

The feasibility of measuring calprotectin from a throat swab as a marker of infections caused by group A streptococcus: a case-control feasibility study.

BACKGROUND: Most people with sore throat do not benefit from antibiotic treatment, but nearly three-quarters of those presenting in primary care are prescribed antibiotics. A test that is predictive of bacterial infection could help guide antibiotic prescribing. Calprotectin is a biomarker of neutrophilic inflammation, and may be a useful marker of bacterial throat infections. AIM: To assess the feasibility of measuring calprotectin from throat swabs, and assess whether individuals with sore throats likely to be caused by streptococcal infections have apparently higher throat calprotectin levels than other individuals with sore throat and healthy volunteers. DESIGN & SETTING: A proof of concept case-control study was undertaken, which compared primary care patients with sore throats and healthy volunteers. METHOD: Baseline characteristics and throat swabs were collected from 30 primary care patients with suspected streptococcal sore throat, and throat swabs were taken from 10 volunteers without sore throat. Calprotectin level determination and rapid antigen streptococcal testing were conducted on the throat swab eluents. Calprotectin levels in the following groups were compared: volunteers without a sore throat; all patients with a sore throat; patients with a sore throat testing either negative or positive for streptococcal antigen; and those with lower and higher scores on clinical prediction rules for streptococcal sore throat. RESULTS: Calprotectin was detected in all throat swab samples. Mean calprotectin levels were numerically higher in patients with sore throat compared with healthy volunteers, and sore throat patients who had group A streptococci antigen detected compared with those who did not. CONCLUSION: Calprotectin can be measured from throat swab samples and levels are consistent with the hypothesis that streptococcal infection leads to higher throat calprotectin levels. This hypothesis will be tested in a larger study.

C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations.

BACKGROUND: Point-of-care testing of C-reactive protein (CRP) may be a way to reduce unnecessary use of antibiotics without harming patients who have acute exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: We performed a multicenter, open-label, randomized, controlled trial involving patients with a diagnosis of COPD in their primary care clinical record who consulted a clinician at 1 of 86 general medical practices in England and Wales for an acute exacerbation of COPD. The patients were assigned to receive usual care guided by CRP point-of-care testing (CRP-guided group) or usual care alone (usual-care group). The primary outcomes were patient-reported use of antibiotics for acute exacerbations of COPD within 4 weeks after randomization (to show superiority) and COPD-related health status at 2 weeks after randomization, as measured by the Clinical COPD Questionnaire, a 10-item scale with scores ranging from 0 (very good COPD health status) to 6 (extremely poor COPD health status) (to show noninferiority). RESULTS: A total of 653 patients underwent randomization. Fewer patients in the CRP-guided group reported antibiotic use than in the usual-care group (57.0% vs. 77.4%; adjusted odds ratio, 0.31; 95% confidence interval [CI], 0.20 to 0.47). The adjusted mean difference in the total score on the Clinical COPD Questionnaire at 2 weeks was -0.19 points (two-sided 90% CI, -0.33 to -0.05) in favor of the CRP-guided group. The antibiotic prescribing decisions made by clinicians at the initial consultation were ascertained for all but 1 patient, and antibiotic prescriptions issued over the first 4 weeks of follow-up were ascertained for 96.9% of the patients. A lower percentage of patients in the CRP-guided group than in the usual-care group received an antibiotic prescription at the initial consultation (47.7% vs. 69.7%, for a difference of 22.0 percentage points; adjusted odds ratio, 0.31; 95% CI, 0.21 to 0.45) and during the first 4 weeks of follow-up (59.1% vs. 79.7%, for a difference of 20.6 percentage points; adjusted odds ratio, 0.30; 95% CI, 0.20 to 0.46). Two patients in the usual-care group died within 4 weeks after randomization from causes considered by the investigators to be unrelated to trial participation. CONCLUSIONS: CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm. (Funded by the National Institute for Health Research Health Technology Assessment Program; PACE Current Controlled Trials number, ISRCTN24346473.).

A prospective pilot study of thigh-administered intermittent pneumatic compression in the management of hard-to-heal lower limb venous and mixed aetiology ulcers.

This was a prospective observational pilot study of a unique intermittent pneumatic compression (IPC) device designed to be applied in the thigh region of the affected limb in patients with lower limb ulceration of both venous and mixed (venous and arterial) aetiologies. This compression system consists of a circumferential three-chamber thigh garment and an electronic pneumatic compression pump operating over a repeated 4-minute cycle. Patients were recruited from outpatient wound clinics. Those recruited were treated with standard therapy in addition to IPC, which was applied for 2 hours per day, and followed up for a total of 8 weeks. The primary objective of the study was to examine the effects of IPC on wound healing over an 8-week period. The other objectives were to assess patients' experiences of pain and the acceptability of IPC device. Twenty-one patients were recruited, and wounds progressed towards healing in 95.24% (20/21) of the patients. Pain scores decreased in 83.33% (15/18) of the patients. Most patients felt that the thigh-applied IPC device was comfortable and easy to apply and remove. The thigh-administered IPC device can be recommended for use in routine clinical practice, especially when other treatment options are limited.

Antibiotic prescribing quality for children in primary care: an observational study.

BACKGROUND: Overuse and inappropriate prescribing of antibiotics is driving antibiotic resistance. GPs often prescribe antibiotics for upper respiratory tract infections (URTIs) in young children despite their marginal beneficial effects. AIM: To assess the quality of antibiotic prescribing for common infections in young children attending primary care and to investigate influencing factors. DESIGN AND SETTING: An observational, descriptive analysis, including children attending primary care sites in England and Wales. METHOD: The Diagnosis of Urinary Tract infection in Young children study collected data on 7163 children aged <5 years, presenting to UK primary care with an acute illness (<28 days). Data were compared with the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) disease-specific quality indicators to assess prescribing for URTIs, tonsillitis, and otitis media, against ESAC-Net proposed standards. Non-parametric trend tests and χ2 tests assessed trends and differences in prescribing by level of deprivation, site type, and demographics. RESULTS: Prescribing rates fell within the recommendations for URTIs but exceeded the recommended limits for tonsillitis and otitis media. The proportion of children receiving the recommended antibiotic was below standards for URTIs and tonsillitis, but within the recommended limits for otitis media. Prescribing rates increased as the level of deprivation decreased for all infections (P<0.05), and increased as the age of the child increased for URTIs and tonsillitis (P<0.05). There were no other significant trends or differences. CONCLUSION: The quality of antibiotic prescribing in this study was mixed and highlights the scope for future improvements. There is a need to assess further the quality of disease-specific antibiotic prescribing in UK primary care settings using data representative of routine clinical practice.

General practitioner use of a C-reactive protein point-of-care test to help target antibiotic prescribing in patients with acute exacerbations of chronic obstructive pulmonary disease (the PACE study): study protocol for a randomised controlled trial.

BACKGROUND: Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed an antibiotic, which may not always be appropriate and may cause harm. C-reactive protein (CRP) is an acute-phase biomarker that can be rapidly measured at the point of care and may predict benefit from antibiotic treatment in AECOPD. It is not clear whether the addition of a CRP point-of-care test (POCT) to clinical assessment leads to a reduction in antibiotic consumption without having a negative impact on COPD health status. METHODS/DESIGN: This is a multicentre, individually randomised controlled trial (RCT) aiming to include 650 participants with a diagnosis of AECOPD in primary care. Participants will be randomised to be managed according to usual care (control) or with the addition of a CRP POCT to guide antibiotic prescribing. Antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status (total score) measured by the Clinical COPD Questionnaire (CCQ) at 2 weeks post randomisation will be co-primary outcomes. Primary analysis (by intention-to-treat) will determine differences in antibiotic consumption for superiority and COPD health status for non-inferiority. Secondary outcomes include: COPD health status, CCQ domain scores, use of other COPD treatments (weeks 1, 2 and 4), EQ-5D utility scores (weeks 1, 2 and 4 and month 6), disease-specific, health-related quality of life (HRQoL) at 6 months, all-cause antibiotic consumption (antibiotic use for any condition) during first 4 weeks post randomisation, total antibiotic consumption (number of days during first 4 weeks of antibiotic consumed for AECOPD/any reason), antibiotic prescribing at the index consultation and during following 4 weeks, adverse effects over the first 4 weeks, incidence of pneumonia (weeks 4 and 6 months), health care resource use and cost comparison over the 6 months following randomisation. Prevalence and resistance profiles of bacteria will be assessed using throat and sputum samples collected at baseline and 4-week follow-up. A health economic evaluation and qualitative process evaluation will be carried out. DISCUSSION: If shown to be effective (i.e. leads to a reduction in antibiotic use with no worse COPD health status), the use of the CRP POCT could lead to better outcomes for patients with AECOPD and help reduce selective pressures driving the development of antimicrobial resistance. PACE will be one of the first studies to evaluate the cost-effectiveness of a POCT biomarker to guide clinical decision-making in primary care on patient-reported outcomes, antibiotic prescribing and antibiotic resistance for AECOPD. TRIAL REGISTRATION: ISRCTN registry, ID: ISRCTN24346473 . Registered on 20 August 2014.

Personalised risk communication for informed decision making about taking screening tests.

BACKGROUND: There is a trend towards greater patient involvement in healthcare decisions. Although screening is usually perceived as good for the health of the population, there are risks associated with the tests involved. Achieving both adequate involvement of consumers and informed decision making are now seen as important goals for screening programmes. Personalised risk estimates have been shown to be effective methods of risk communication. OBJECTIVES: To assess the effects of personalised risk communication on informed decision making by individuals taking screening tests. We also assess individual components that constitute informed decisions. SEARCH METHODS: Two authors searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2012), MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL (EbscoHOST) and PsycINFO (OvidSP) without language restrictions. We searched from 2006 to March 2012. The date ranges for the previous searches were from 1989 to December 2005 for PsycINFO and from 1985 to December 2005 for other databases. For the original version of this review, we also searched CancerLit  and Science Citation Index (March 2001). We also reviewed the reference lists and conducted citation searches of included studies and other systematic reviews in the field, to identify any studies missed during the initial search. SELECTION CRITERIA: Randomised controlled trials incorporating an intervention with a 'personalised risk communication element' for individuals undergoing screening procedures, and reporting measures of informed decisions and also cognitive, affective, or behavioural outcomes addressing the decision by such individuals, of whether or not to undergo screening. DATA COLLECTION AND ANALYSIS: Two authors independently assessed each included trial for risk of bias, and extracted data. We extracted data about the nature and setting of interventions, and relevant outcome data. We used standard statistical methods to combine data using RevMan version 5, including analysis according to different levels of detail of personalised risk communication, different conditions for screening, and studies based only on high-risk participants rather than people at 'average' risk.  MAIN RESULTS: We included 41 studies involving 28,700 people. Nineteen new studies were identified in this update, adding to the 22 studies included in the previous two iterations of the review. Three studies measured informed decision with regard to the uptake of screening following personalised risk communication as a part of their intervention. All of these three studies were at low risk of bias and there was strong evidence that the interventions enhanced informed decision making, although with heterogeneous results. Overall 45.2% (592/1309) of participants who received personalised risk information made informed choices, compared to 20.2% (229/1135) of participants who received generic risk information. The overall odds ratios (ORs) for informed decision were 4.48 (95% confidence interval (CI) 3.62 to 5.53 for fixed effect) and 3.65 (95% CI 2.13 to 6.23 for random effects). Nine studies measured increase in knowledge, using different scales. All of these studies showed an increase in knowledge with personalised risk communication. In three studies the interventions showed a trend towards more accurate risk perception, but the evidence was of poor quality. Four out of six studies reported non-significant changes in anxiety following personalised risk communication to the participants. Overall there was a small non-significant decrease in the anxiety scores. Most studies (32/41) measured the uptake of screening tests following interventions. Our results (OR 1.15 (95% CI 1.02 to 1.29)) constitute low quality evidence, consistent with a small effect, that personalised risk communication in which a risk score was provided (6 studies) or the participants were given their categorised risk (6 studies), increases uptake of screening tests.  AUTHORS' CONCLUSIONS: There is strong evidence from three trials that personalised risk estimates incorporated within communication interventions for screening programmes enhance informed choices. However the evidence for increasing the uptake of such screening tests with similar interventions is weak, and it is not clear if this increase is associated with informed choices. Studies included a diverse range of screening programmes. Therefore, data from this review do not allow us to draw conclusions about the best interventions to deliver personalised risk communication for enhancing informed decisions. The results are dominated by findings from the topic area of mammography and colorectal cancer. Caution is therefore required in generalising from these results, and particularly for clinical topics other than mammography and colorectal cancer screening.