Design of proxy indicators estimating the appropriateness of antibiotics prescribed by French dentists: a cross-sectional study based on reimbursement data.

Background - The literature shows that the prescription of antibiotics in dental care is often unnecessary or inappropriate. Indicators estimating the appropriateness of antibiotics prescribed by dentists based on routine databases are however not available in the literature. Our objectives were to: (i) design proxy indicators estimating the appropriateness of antibiotics prescribed by dentists; (ii) evaluate their clinimetric properties; and (iii) provide results for these proxy indicators for dentists located in a north-eastern French region.Methods - We selected and adapted proxy indicators from the literature. Using 2019 Regional Health Insurance data, we evaluated the proxy indicators' clinimetric properties (measurability, applicability, and potential room for improvement), their results with performance scores (% of dentists who reached the target value), and the case-mix stability.Results - We included 3,014 general dental practitioners, who prescribed a total of 373,975 antibiotics to 308,123 patients in 2019. We identified four proxy indicators estimating antibiotic prescribing appropriateness in dental care. All proxy indicators had good clinimetric properties. Performance scores were generally low (10.5 to 73.0%, depending on the indicator), suggesting an important room for improvement. These results showed large variations between dentists (large interquartile ranges) and according to the patients' characteristics (case-mix stability).Conclusion - These four proxy indicators might be used to guide antibiotic stewardship interventions in dental care.

Considerable doubt about rubella screening and vaccination among unvaccinated orthodox protestant women: a mixed-methods study.

BACKGROUND: Women who are susceptible to rubella are advised to vaccinate against rubella to prevent infection in future pregnancies, and thus avert the risk of congenital rubella syndrome in their unborn child. Rubella outbreaks periodically occur in the under-vaccinated orthodox Protestant community in the Netherlands. The objective of this mixed-methods study was to determine and understand personal experience with rubella, perceived rubella susceptibility, and intention to accept rubella screening and vaccination among unvaccinated orthodox Protestant women. The ultimate aim of this study was to inform policy and practice and contribute to the prevention of cases of congenital rubella syndrome. METHODS: A mixed-methods study was conducted combining an online survey and semi-structured interviews among unvaccinated Dutch orthodox Protestant women aged 18-40 years. Descriptive analysis was used for quantitative data. Qualitative data was analysed using codes and categories. RESULTS: Results of the survey (167 participants) showed that most participants had personal experience with rubella (74%, 123/167) and 101 women (61%, 101/167) indicated they had had rubella themselves. More than half of the women were undecided whether to accept rubella susceptibility screening (56%; 87/156) or rubella vaccination (55%; 80/146). Qualitative findings (10 participants) showed that most women thought they were not susceptible to rubella. Indecisiveness and negative attitudes to accept rubella vaccination were related with religious arguments to object vaccination and with women's perception of absence of imminent threat of rubella. Furthermore, results showed presence of misconceptions among women in the interpretation of their susceptibility and high confidence in their parents' memory that they had experienced rubella as a child although no laboratory screening had been conducted. CONCLUSIONS: In light of an imminent rubella outbreak in the Netherlands, a tailored education campaign should be prepared aimed at and established in cooperation with the under-vaccinated orthodox Protestant community. Health care providers should provide adequate information on rubella and support decision-making in order to stimulate women to make a deliberate and informed decision on rubella screening and, if necessary, subsequent vaccination.

Why we prescribe antibiotics for too long in the hospital setting: a systematic scoping review.

BACKGROUND: In daily hospital practice, antibiotic therapy is commonly prescribed for longer than recommended in guidelines. Understanding the key drivers of prescribing behaviour is crucial to generate meaningful interventions to bridge this evidence-to-practice gap. OBJECTIVES: To identify behavioural determinants that might prevent or enable improvements in duration of antibiotic therapy in daily practice. METHODS: We systematically searched PubMed, Embase, PsycINFO and Web of Science for relevant studies that were published between January 2000 and August 2021. All qualitative, quantitative and mixed-method studies in adults in a hospital setting that reported determinants of antibiotic therapy duration were included. RESULTS: Twenty-two papers were included in this review. A first set of studies provided 82 behavioural determinants that shape how health professionals make decisions about duration; most of these were related to individual health professionals' knowledge, skills and cognitions, and to professionals' interactions. A second set of studies provided 17 determinants that point to differences in duration regarding various pathogens, diseases, or patient, professional or hospital department characteristics, but do not explain why or how these differences occur. CONCLUSIONS: Limited literature is available describing a wide range of determinants that influence duration of antibiotic therapy in daily practice. This review provides a stepping stone for the development of stewardship interventions to optimize antibiotic therapy duration, but more research is warranted. Stewardship teams must develop complex improvement interventions to address the wide variety of behavioural determinants, adapted to the specific pathogen, disease, patient, professional and/or hospital department involved.

Quantity Metrics and Proxy Indicators to Estimate the Volume and Appropriateness of Antibiotics Prescribed in French Nursing Homes: A Cross-sectional Observational Study Based on 2018 Reimbursement Data.

BACKGROUND: Antibiotic resistance is an increasing threat to public health globally. Indicators on antibiotic prescribing are required to guide antibiotic stewardship interventions in nursing homes. However, such indicators are not available in the literature. Our main objective was to provide a set of quantity metrics and proxy indicators to estimate the volume and appropriateness of antibiotic use in nursing homes. METHODS: Recently published articles were first used to select quantity metrics and proxy indicators, which were adapted to the French nursing home context. A cross-sectional observational study was then conducted based on reimbursement databases. We included all community-based nursing homes of the Lorraine region in northeastern France. We present descriptive statistics for quantity metrics and proxy indicators. For proxy indicators, we also assessed performance scores, clinimetric properties (measurability, applicability, and room for improvement), and conducted case-mix and cluster analyses. RESULTS: A total of 209 nursing homes were included. We selected 15 quantity metrics and 11 proxy indicators of antibiotic use. The volume of antibiotic use varied greatly between nursing homes. Proxy indicator performance scores were low, and variability between nursing homes was high for all indicators, highlighting important room for improvement. Six of the 11 proxy indicators had good clinimetric properties. Three distinct clusters were identified according to the number of proxy indicators for which the acceptable target was reached. CONCLUSIONS: This set of 15 quantity metrics and 11 proxy indicators may be adapted to other contexts and could be used to guide antibiotic stewardship programs in nursing homes.

Tricyclic antidepressants for major depressive disorder: a comprehensive evaluation of current practice in the Netherlands.

BACKGROUND: Traditionally tricyclic antidepressants (TCAs) have an important place in treatment of major depressive disorder (MDD). Today, often other antidepressant medications are considered as first step in the pharmacological treatment of MDD, mainly because they are associated with less adverse effects, whereby the position of TCAs appears unclear. In this study we aimed to examine the current practice of TCAs in treatment of unipolar MDD. METHODS: A mixed methods approach was applied. First, a selection of leading international and national guidelines was reviewed. Second, actual TCA prescription was examined by analyzing health records of 75 MDD patients treated with the TCAs nortriptyline, clomipramine or imipramine in different centers in the Netherlands. Third, promotors and barriers influencing the choice for TCAs and dosing strategies were explored using semi-structured interviews with 24 Dutch psychiatrists. RESULTS: Clinical practice guidelines were sometimes indirective and inconsistent with each other. Health records revealed that most patients (71%) attained therapeutic plasma concentrations within two months of TCA use. Patients who achieved therapeutic plasma concentrations reached them on average after 19.6 days (SD 10.9). Both health records and interviews indicated that therapeutic nortriptyline concentrations were attained faster compared to other TCAs. Various factors were identified influencing the choice for TCAs and dosing by psychiatrists. CONCLUSIONS: Guideline recommendations and clinical practice regarding TCA prescription for MDD vary. To increase consistency in clinical practice we recommend development of an up-to-date guideline integrating selection and dosing of TCAs, including the roles of therapeutic drug monitoring and pharmacogenetics. Such a guideline is currently lacking and would contribute to optimal TCA treatment, whereby efficacy and tolerability may be increased.

Quality Indicators for Appropriate Outpatient Parenteral Antimicrobial Therapy in Adults: A Systematic Review and RAND-modified Delphi Procedure.

BACKGROUND: Our aim in this study was to develop quality indicators (QIs) for outpatient parenteral antimicrobial therapy (OPAT) care that can be used as metrics for quality assessment and improvement. METHODS: A RAND-modified Delphi procedure was used to develop a set of QIs. Recommendations on appropriate OPAT care in adults were retrieved from the literature using a systematic review and translated into potential QIs. These QIs were appraised and prioritized by a multidisciplinary panel of international OPAT experts in 2 questionnaire rounds combined with a meeting between rounds. RESULTS: The procedure resulted in 33 OPAT-specific recommendations. The following QIs that describe recommended OPAT care were prioritized by the expert panel: the presence of a structured OPAT program, a formal OPAT care team, a policy on patient selection criteria, and a treatment and monitoring plan; assessment for OPAT should be performed by the OPAT team; patients and family should be informed about OPAT; there should be a mechanism in place for urgent discussion and review of emergent clinical problems, and a system in place for rapid communication; laboratory results should be delivered to physicians within 24 hours; and the OPAT team should document clinical response to antimicrobial management, document adverse events, and monitor QIs for OPAT care and make these data available. CONCLUSIONS: We systematically developed a set of 33 QIs for optimal OPAT care, of which 12 were prioritized by the expert panel. These QIs can be used to assess and improve the quality of care provided by OPAT teams.

Prostate biopsy techniques and pre-biopsy prophylactic measures: variation in current practice patterns in the Netherlands.

BACKGROUND: The clinical landscape of prostate biopsy (PB) is evolving with changes in procedures and techniques. Moreover, antibiotic resistance is increasing and influences the efficacy of pre-biopsy prophylactic regimens. Therefore, increasing antibiotic resistance may impact on clinical care, which probably results in differences between hospitals. The objective of our study is to determine the (variability in) current practices of PB in the Netherlands and to gain insight into Dutch urologists' perceptions of fluoroquinolone resistance and biopsy related infections. METHODS: An online questionnaire was prepared using SurveyMonkey® platform and distributed to all 420 members of the Dutch Association of Urology, who work in 81 Dutch hospitals. Information about PB techniques and periprocedural antimicrobial prophylaxis was collected. Urologists' perceptions regarding pre-biopsy antibiotic prophylaxis in an era of antibiotic resistance was assessed. Descriptive statistical analysis was performed. RESULTS: One hundred sixty-one responses (38.3%) were analyzed representing 65 (80.3%) of all Dutch hospitals performing PB. Transrectal ultrasound guided prostate biopsy (TRUSPB) was performed in 64 (98.5%) hospitals. 43.1% of the hospitals (also) used other image-guided biopsy techniques. Twenty-three different empirical prophylactic regimens were reported among the hospitals. Ciprofloxacin was most commonly prescribed (84.4%). The duration ranged from one pre-biopsy dose (59.4%) to 5 days extended prophylaxis. 25.2% of the urologists experienced ciprofloxacin resistance as a current problem in the prevention of biopsy related infections and 73.6% as a future problem. CONCLUSIONS: There is a wide variation in practice patterns among Dutch urologists. TRUSPB is the most commonly used biopsy technique, but other image-guided biopsy techniques are increasingly used. Antimicrobial prophylaxis is not standardized and prolonged prophylaxis is common. The wide variation in practice patterns and lack of standardization underlines the need for evidence-based recommendations to guide urologists in choosing appropriate antimicrobial prophylaxis for PB in the context of increasing antibiotic resistance.

Ensuring Antibiotic Development, Equitable Availability, and Responsible Use of Effective Antibiotics: Recommendations for Multisectoral Action.

Antibiotic resistance is a growing threat to global public health. The World Health Organization's Global Action Plan on Antimicrobial Resistance recommends engaging multisectoral stakeholders to tackle the issue. However, so far, few studies have addressed barriers to antibiotic development, equitable availability, and responsible antibiotic use from the perspective of stakeholders outside healthcare facilities or patient communities: the so-called third-party stakeholders. Third-party stakeholders include, inter alia, governments, regulatory agencies, and professionals working in antibiotic research and development and medical ethics. This viewpoint provides an overview of barriers to antibiotic development, equitable availability of effective antibiotics, and the responsible use of antibiotics. The barriers were identified in an exploratory, qualitative interview study with an illustrative sample of 12 third-party stakeholders. Recommendations to lift these barriers are presented, together with examples of recently-made progress. The recommendations should guide future antibiotic policies and multisectoral policy action.

Development of quality indicators for the management of Staphylococcus aureus bacteraemia.

BACKGROUND: Staphylococcus aureus bacteraemia (SAB) is a serious and often fatal infectious disease. The quality of management of SAB is modifiable and can thus affect the outcome. Quality indicators (QIs) can be used to measure the quality of care of the various aspects of SAB management in hospitals, enabling professionals to identify targets for improvement and stimulating them to take action. OBJECTIVES: To develop QIs for the management of hospitalized patients with SAB. METHODS: A RAND-modified Delphi procedure was used to develop a set of QIs for the management of SAB in hospitalized patients. First, available QIs for the management of SAB were extracted from the literature published since 1 January 2000 (MEDLINE and Embase databases). Thereafter, an international multidisciplinary expert panel appraised these QIs during two questionnaire rounds with an intervening face-to-face meeting. RESULTS: The literature search resulted in a list of 39 potential QIs. After appraisal by 30 medical specialists, 25 QIs describing recommended care at patient level were selected. These QIs defined appropriate follow-up blood cultures (n=2), echocardiography (n=6), source control (n=4), antibiotic therapy (n=7), antibiotic dose adjustment (n=2), intravenous-to-oral switch (n=2), infectious disease consultation (n=1) and medical discharge report (n=1). CONCLUSIONS: A set of 25 QIs for the management of SAB for hospitalized patients was developed by using a RAND-modified Delphi procedure among international experts. These QIs can measure the quality of various aspects of SAB management. This information can be fed back to the relevant stakeholders in order to identify improvement targets and optimize care.

Down-titration and discontinuation strategies of tumour necrosis factor-blocking agents for rheumatoid arthritis in patients with low disease activity.

BACKGROUND: Anti-tumour necrosis factor (TNF) agents are effective in treating people with rheumatoid arthritis (RA), but are associated with (dose-dependent) adverse effects and high costs. To prevent overtreatment, several trials have assessed the effectiveness of down-titration compared with continuation of the standard dose. This is an update of a Cochrane Review published in 2014. OBJECTIVES: To evaluate the benefits and harms of down-titration (dose reduction, discontinuation, or disease activity-guided dose tapering) of anti-TNF agents on disease activity, functioning, costs, safety, and radiographic damage compared with usual care in people with RA and low disease activity. SEARCH METHODS: We searched MEDLINE, Embase, Web of Science and CENTRAL (29 March 2018) and four trial registries (11 April 2018) together with reference checking, citation searching, and contact with study authors to identify additional studies. We screened conference proceedings (American College of Rheumatology and European League Against Rheumatism 2005-2017). SELECTION CRITERIA: Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing down-titration (dose reduction, discontinuation, disease activity-guided dose tapering) of anti-TNF agents (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) to usual care/no down-titration in people with RA and low disease activity. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: One previously included trial was excluded retrospectively in this update because it was not an RCT/CCT. We included eight additional trials, for a total of 14 studies (13 RCTs and one CCT, 3315 participants in total) reporting anti-TNF down-titration. Six studies (1148 participants) reported anti-TNF dose reduction compared with anti-TNF continuation. Eight studies (2111 participants) reported anti-TNF discontinuation compared with anti-TNF continuation (three studies assessed both anti-TNF discontinuation and dose reduction), and three studies assessed disease activity-guided anti-TNF dose tapering (365 participants). These studies included data on all anti-TNF agents, but primarily adalimumab and etanercept. Thirteen studies were available in full text, one was available as abstract. We assessed the included studies generally at low to moderate risk of bias; our main concerns were bias due to open-label treatment and unblinded outcome assessment. Clinical heterogeneity between the trials was high. The included studies were performed at clinical centres around the world and included people with early as well as established RA, the majority of whom were female with mean ages between 47 and 60. Study durations ranged from 6 months to 3.5 years.We found that anti-TNF dose reduction leads to little or no difference in mean disease activity score (DAS28) after 26 to 52 weeks (high-certainty evidence, mean difference (MD) 0.06, 95% confidence interval (CI) -0.11 to 0.24, absolute risk difference (ARD) 1%) compared with continuation. Also, anti-TNF dose reduction does not result in an important deterioration in function after 26 to 52 weeks (Health Assessment Questionnaire Disability Index (HAQ-DI)) (high-certainty evidence, MD 0.09, 95% CI 0.00 to 0.19, ARD 3%). Next to this, anti-TNF dose reduction may slightly reduce the proportion of participants switched to another biologic (low-certainty evidence), but probably slightly increases the proportion of participants with minimal radiographic progression after 52 weeks (moderate-certainty evidence, risk ratio (RR) 1.22, 95% CI 0.76 to 1.95, ARD 2% higher). Anti-TNF dose reduction may cause little or no difference in serious adverse events, withdrawals due to adverse events and proportion of participants with persistent remission (low-certainty evidence).Results show that anti-TNF discontinuation probably slightly increases the mean disease activity score (DAS28) after 28 to 52 weeks (moderate-certainty evidence, MD 0.96, 95% CI 0.67 to 1.25, ARD 14%), and that the RR of persistent remission lies between 0.16 and 0.77 (low-certainty evidence). Anti-TNF discontinuation increases the proportion participants with minimal radiographic progression after 52 weeks (high-certainty evidence, RR 1.69, 95% CI 1.10 to 2.59, ARD 7%) and may lead to a slight deterioration in function (HAQ-DI) (low-certainty evidence). It is uncertain whether anti-TNF discontinuation influences the number of serious adverse events (due to very low-certainty evidence) and the number of withdrawals due to adverse events after 28 to 52 weeks probably increases slightly (moderate-certainty evidence, RR 1.46, 95% CI 0.75 to 2.84, ARD 1% higher).Anti-TNF disease activity-guided dose tapering may result in little or no difference in mean disease activity score (DAS28) after 72 to 78 weeks (low-certainty evidence). Furthermore, anti-TNF disease activity-guided dose tapering results in little or no difference in the proportion of participants with persistent remission after 18 months (high-certainty evidence, RR 0.89, 95% CI 0.75 to 1.06, ARD -9%) and may result in little or no difference in switching to another biologic (low-certainty evidence). Anti-TNF disease activity-guided dose tapering may slightly increase proportion of participants with minimal radiographic progression (low-certainty evidence) and probably leads to a slight deterioration of function after 18 months (moderate-certainty evidence, MD 0.2 higher, 0.02 lower to 0.42 higher, ARD 7% higher), It is uncertain whether anti-TNF disease activity-guided dose tapering influences the number of serious adverse events due to very low-certainty evidence. AUTHORS' CONCLUSIONS: We found that fixed-dose reduction of anti-TNF, after at least three to 12 months of low disease activity, is comparable to continuation of the standard dose regarding disease activity and function, and may be comparable with regards to the proportion of participants with persistent remission. Discontinuation (also without disease activity-guided adaptation) of anti-TNF is probably inferior to continuation of treatment with respect to disease activity, the proportion of participants with persistent remission, function, and minimal radiographic damage. Disease activity-guided dose tapering of anti-TNF is comparable to continuation of treatment with respect to the proportion of participants with persistent remission and may be comparable regarding disease activity.Caveats of this review are that available data are mainly limited to etanercept and adalimumab, the heterogeneity between studies, and the use of superiority instead of non-inferiority designs.Future research should focus on the anti-TNF agents infliximab and golimumab; assessment of disease activity, function, and radiographic outcomes after longer follow-up; and assessment of long-term safety, cost-effectiveness, and predictors for successful down-titration. Also, use of a validated flare criterion, non-inferiority designs, and disease activity-guided tapering instead of fixed-dose reduction or discontinuation would allow researchers to better interpret study findings and generalise to clinical practice.

Towards a global definition of responsible antibiotic use: results of an international multidisciplinary consensus procedure.

Background: Conducted as part of the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project, this study aimed to identify key elements for a global definition of responsible antibiotic use based on diverse stakeholder input. Methods: A three-step RAND-modified Delphi method was applied. First, a systematic review of antibiotic stewardship literature and relevant organization web sites identified definitions and synonyms of responsible use. Identified elements of definitions were presented by questionnaire to a multidisciplinary international stakeholder panel for appraisal of their relevance. Finally, questionnaire results were discussed in a consensus meeting. Results: The systematic review and the web site search identified 17 synonyms (e.g. appropriate, correct) and 22 potential elements to include in a definition of responsible use. Elements were grouped into patient-level (e.g. Indication, Documentation) or societal-level elements (e.g. Education, Future Effectiveness). Forty-eight stakeholders with diverse backgrounds [medical community, public health, patients, antibiotic research and development (R&D), regulators, governments] from 18 countries across all continents participated in the questionnaire. Based on relevance scores, 21 elements were retained, 9 were rephrased and 1 was added. Together, the 22 elements and associated best-practice descriptions comprise an exhaustive list of elements to be considered when defining responsible use. Conclusions: Combination of concepts from the literature and stakeholder opinion led to an international multidisciplinary consensus on a global definition of responsible antibiotic use. The widely diverging perspectives of stakeholders providing input should ensure the comprehensiveness and relevance of the definition for both individual patients and society. An aspirational goal would be to address all elements.

Quality indicators assessing antibiotic use in the outpatient setting: a systematic review followed by an international multidisciplinary consensus procedure.

Objectives: Quality indicators (QIs) assessing the appropriateness of antibiotic use are essential to identify targets for improvement and guide antibiotic stewardship interventions. The aim of this study was to develop a set of QIs for the outpatient setting from a global perspective. Methods: A systematic literature review was performed by searching MEDLINE and relevant web sites in order to retrieve a list of QIs. These indicators were extracted from published trials, guidelines, literature reviews or consensus procedures. This evidence-based set of QIs was evaluated by a multidisciplinary, international group of stakeholders using a RAND-modified Delphi procedure, using two online questionnaires and a face-to-face meeting between them. Stakeholders appraised the QIs' relevance using a nine-point Likert scale. This work is part of the DRIVE-AB project. Results: The systematic literature review identified 43 unique QIs, from 54 studies and seven web sites. Twenty-five stakeholders from 14 countries participated in the consensus procedure. Ultimately, 32 QIs were retained, with a high level of agreement. The set of QIs included structure, process and outcome indicators, targeting both high- and middle- to low-income settings. Most indicators focused on general practice, addressing the common indications for antibiotic use in the community (particularly urinary and respiratory tract infections), and the organization of healthcare facilities. Twelve indicators specifically addressed outpatient parenteral antimicrobial therapy (OPAT). Conclusions: We identified a set of 32 outpatient QIs to measure the appropriateness of antibiotic use. These QIs can be used to identify targets for improvement and to evaluate the effects of antibiotic stewardship interventions.

Metrics to assess the quantity of antibiotic use in the outpatient setting: a systematic review followed by an international multidisciplinary consensus procedure.

Background: The international Innovative Medicines Initiative (IMI) project DRIVE-AB (Driving Reinvestment in Research and Development and Responsible Antibiotic Use) aims to develop a global definition of 'responsible' antibiotic use. Objectives: To identify consensually validated quantity metrics for antibiotic use in the outpatient setting. Methods: First, outpatient quantity metrics (OQMs) were identified by a systematic search of literature and web sites published until 12 December 2014. Identified OQMs were evaluated by a multidisciplinary, international stakeholder panel using a RAND-modified Delphi procedure. Two online questionnaires and a face-to-face meeting between them were conducted to assess OQM relevance for measuring the quantity of antibiotic use on a nine-point Likert scale, to add comments or to propose new metrics. Results: A total of 597 articles were screened, 177 studies met criteria for full-text screening and 138 were finally included. Twenty different OQMs were identified and appraised by 23 stakeholders. During the first survey, 14 OQMs were excluded and 6 qualified for discussion. During the face-to-face meeting, 10 stakeholders retained five OQMs and suggestions were made considering context and combination of metrics. The final set of metrics included defined daily doses, treatments/courses and prescriptions per defined population, treatments/courses and prescriptions per defined number of physician contacts and seasonal variation of total antibiotic use. Conclusions: A small set of consensually validated metrics to assess the quantity of antibiotic use in the outpatient setting was obtained, enabling (inter)national comparisons. The OQMs will help build a global conceptual framework for responsible antibiotic use.

Quality indicators for responsible antibiotic use in the inpatient setting: a systematic review followed by an international multidisciplinary consensus procedure.

Background: This study was conducted as part of the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project and aimed to develop generic quality indicators (QIs) for responsible antibiotic use in the inpatient setting. Methods: A RAND-modified Delphi method was applied. First, QIs were identified by a systematic review. A complementary search was performed on web sites of relevant organizations. Duplicates were removed and disease and patient-specific QIs were combined into generic indicators. The relevance of these QIs was appraised by a multidisciplinary international stakeholder panel through two questionnaires and an in-between consensus meeting. Results: The systematic review retrieved 70 potential generic QIs. The QIs were appraised by 25 international stakeholders with diverse backgrounds (medical community, public health, patients, antibiotic research and development, regulators, governments). Ultimately, 51 QIs were selected in consensus. QIs with the highest relevance score included: (i) an antibiotic plan should be documented in the medical record at the start of the antibiotic treatment; (ii) the results of bacteriological susceptibility testing should be documented in the medical record; (iii) the local guidelines should correspond to the national guidelines but should be adapted based on local resistance patterns; (iv) an antibiotic stewardship programme should be in place at the healthcare facility; and (v) allergy status should be taken into account when antibiotics are prescribed. Conclusions: This systematic and stepwise method combining evidence from literature and stakeholder opinion led to multidisciplinary international consensus on generic inpatient QIs that can be used globally to assess the quality of antibiotic use.

Variation in antibiotic use among and within different settings: a systematic review.

Objectives: Variation in antibiotic use may reflect inappropriate use. We aimed to systematically describe the variation in measures for antibiotic use among settings or providers. This study was conducted as part of the innovative medicines initiative (IMI)-funded international project DRIVE-AB. Methods: We searched for studies published in MEDLINE from January 2004 to January 2015 reporting variation in measures for systemic antibiotic use (e.g. DDDs) in inpatient and outpatient settings. The ratio between a study's reported maximum and minimum values of a given measure [maximum:minimum ratio (MMR)] was calculated as a measure of variation. Similar measures were grouped into categories and when possible the overall median ratio and IQR were calculated. Results: One hundred and forty-three studies were included, of which 85 (59.4%) were conducted in Europe and 12 (8.4%) in low- to middle-income countries. Most studies described the variation in the quantity of antibiotic use in the inpatient setting (81/143, 56.6%), especially among hospitals (41/81, 50.6%). The most frequent measure was DDDs with different denominators, reported in 23/81 (28.4%) inpatient studies and in 28/62 (45.2%) outpatient studies. For this measure, we found a median MMR of 3.7 (IQR 2.6-5.0) in 4 studies reporting antibiotic use in ICUs in DDDs/1000 patient-days and a median MMR of 2.3 (IQR 1.5-3.2) in 18 studies reporting outpatient antibiotic use in DDDs/1000 inhabitant-days. Substantial variation was also identified in other measures. Conclusions: Our review confirms the large variation in antibiotic use even across similar settings and providers. Data from low- and middle-income countries are under-represented. Further studies should try to better elucidate reasons for the observed variation to facilitate interventions that reduce unwarranted practice variation. In addition, the heterogeneity of reported measures clearly shows that there is need for standardization.

Metrics for quantifying antibiotic use in the hospital setting: results from a systematic review and international multidisciplinary consensus procedure.

Background: Quantifying antibiotic use is an essential element of antibiotic stewardship since it allows comparison between different settings and time windows, and measurement of the impact of interventions. However, quantity metrics (QMs) and methods have not been standardized. Objectives: To propose a set of QMs for antibiotic use in inpatients (IQMs) that are accepted globally by professionals in a range of disciplines. The study was conducted within the Driving Reinvestment in Research and Development and Responsible Antibiotic Use (DRIVE-AB) project. Methods: A systematic literature review using MEDLINE identified articles on measuring inpatient antibiotic use, published up to 29 January 2015. A consensually selected list of national and international web sites was screened for additional IQMs. IQMs were classified according to the type of numerator used and presented to a multidisciplinary panel of stakeholders. A RAND-modified Delphi consensus procedure, which consisted of two online questionnaires and a face-to-face meeting, was performed. Results: The systematic literature review and web site search identified 168 eligible articles from which an initial list of 20 IQMs, composed of 20 different numerators and associated denominators was developed. The consensus procedure resulted in a final set of 12 IQMs. Among this final set, DDDs per 100(0) patient-days and days of therapy per patient-days were most frequently found in the review. The panel recommended that antibiotic use should be expressed in at least two metrics simultaneously. Conclusions: Our consensus procedure identified a set of IQMs that we propose as an evidence-based global standard.

Implementation of the EULAR cardiovascular risk management guideline in patients with rheumatoid arthritis: results of a successful collaboration between primary and secondary care.

The updated European League Against Rheumatism (EULAR) guideline recommends cardiovascular disease (CVD) risk assessment at least once every 5 years in all patients with rheumatoid arthritis (RA). This viewpoint starts with a literature overview of studies that investigated the level of CVD risk factor (CVD-RF) screening in patients with RA in general practices or in outpatient clinics. These studies indicate that CVD-RF screening in patients with RA is marginally applied in clinical practice, in primary as well as secondary care. Therefore, the second part of this viewpoint describes an example of the successful implementation of the EULAR cardiovascular disease risk management (CVRM) guideline in patients with RA in a region in the south of the Netherlands where rheumatologists and general practitioners (GPs) closely collaborate to manage the cardiovascular risk of patients with RA. The different components of this collaboration and the responsibilities of respectively primary and secondary care professionals are described. Within this collaboration, lipid profile was used as an indicator to assess whether CVD-RF screening was performed in the previous 5 years. In 72% (n=454) of the 628 patients with RA, a lipid profile was determined in the previous 5 years. As part of routine quality control, a reminder was sent to the GP in case a patient with RA was not screened. After sending the reminder letter, in 88% of all patients with RA, CVD risk assessment was performed. This collaboration can be seen as good practice to provide care in line with the EULAR guideline.

The patient perspective on biologic DMARD dose reduction in rheumatoid arthritis: a mixed methods study.

Objectives: The aim of this study was to identify the factors that play a role for patients with RA when considering dose reduction (i.e. gradual tapering until discontinuation) of biological DMARDs (bDMARDs), and to determine their relative importance. Methods: A mixed methods design was used in which we identified influencing factors by performing semi-structured interviews and ranked these factors using a Maximum Difference Scaling questionnaire. Also, we looked at the influence of several patient characteristics on this ranking. Results: For sub study 1 and 2, 22 and 192 patients with RA were included, respectively, in the analyses. Thirty factors were identified from the interviews-characterized into nine themes-and appraised in the questionnaire. Most respondents had a positive attitude towards bDMARD dose reduction. The study showed that patients are concerned that dose reduction will lead to a disease flare that affects their daily life (pain, function). It is important for them to know that it is possible to increase the dose if (further) reduction fails and that the bDMARD will be effective again. Patients value the opinion of their rheumatologist, and being involved in the decision to start tapering is highly ranked as well. The most important factors were consistent between different groups of patients. Conclusion: The results from this study facilitate implementation of bDMARD dose reduction; they inform care providers on what is important for patients and provide a basis for shared decision making.

Rheumatologists' guideline adherence in rheumatoid arthritis: a randomised controlled study on electronic decision support, education and feedback.

OBJECTIVES: To assess the effects of education, feedback and a computerised decision support system (CDSS) versus education and feedback alone on rheumatologists' rheumatoid arthritis (RA) guideline adherence. METHODS: A single-centre, randomised controlled pilot study was performed among clinicians (rheumatologists, residents and physician assistants; n=20) working at the study centre, with a 1:1 randomisation of included clinicians. A standardized sum score (SSS) on guideline adherence was used as the primary outcome (patient level). The SSS was calculated from 13 dichotomous indicators on quality of RA monitoring, treatment and follow-up. The randomised controlled design was combined with a before-after design in the control group to assess the effect education and feedback alone. RESULTS: Twenty clinicians (mean age 44.3±10.9 years; 55% female) and 990 patients (mean age 62 ± 13 years; 69% female; 72% rheumatoid factor and/or anti-CCP positive) were included. Addition of CDSS to education and feedback did not result in significant better quality of RA care than education and feedback alone (SSS difference 0.02; 95%-CI -0.04 to 0.08; p=0.60). However, before/after comparison showed that education and feedback alone resulted in a significant increase in the SSS from 0.58 to 0.64 (difference 0.06; 95%-CI 0.02 to 0.11; p<0.01). CONCLUSIONS: Our results suggest that CDSS did not have added value with regard to guideline adherence, whereas education and feedback can lead to a small but significant improvement of guideline adherence.

The antibiotic checklist: an observational study of the discrepancy between reported and actually performed checklist items.

BACKGROUND: Checklists are increasingly used to measure quality of care. Recently we implemented an antibiotic checklist in nine Dutch hospitals and showed that use of the checklist resulted in more appropriate antibiotic use. While more appropriate antibiotic use was associated with a reduction in length of stay, use of the checklist in itself was not. In the current study we explored discrepancies between reported and actually performed checklist items at the patient level to test the validity of checklist answers, to evaluate whether discrepancies between reported and actually performed checklist items could explain the lack of effect of checklist use on length of stay, and to identify missed opportunities for performance per checklist item. METHODS: Checklist answers represented reported performance. Actual performance was assessed by data from the patients' medical files. Reported and actually performed checklist items could be 'both YES'; 'both NO'; 'YES reported, NOT actually performed'; or 'NO reported, YES actually performed'. We determined an overall 'both YES' score per checklist, and used mixed models to evaluate whether an association existed between this overall score and patient's length of hospital stay. Finally, we analysed whether the items that were not actually performed, could have been performed. RESULTS: Between January and October 2015 physicians filled in 1207 checklists. In total 7881 items were checked. Most items were 'both YES' (3392/7881, 43.0%) or 'both NO' (2601/7881, 33.0%). The number of 'YES reported, NOT actually performed' items was 1628/7881 (20.7%) compared to 260/7881 (3.3%) 'NO reported, YES actually performed' items. The level of discrepancy between reported and actually performed items differed per checklist item. The item 'prescribe antibiotic treatment according to the local guideline' had the highest percentage of 'YES reported, NOT actually performed' items, namely 45.1%. A higher overall 'both YES' score of the checklist was significantly associated with a shorter length of hospital stay. Of all checklist items 21.8% were not performed while they could have been performed. CONCLUSIONS: Checklist answers do not accurately assess actual provided care. As actual performance of the antibiotic checklist items is associated with length of stay, efforts to increase actual performance appear to be justified.