[Systematic analysis of evaluations of Objective Structured Clinical Exam (OSCE) multiple circuits: Explanatory variables and inter-rater correlations]. / Analyse systématique des évaluations de circuits multiples d'examen clinique objectif structuré (ECOS) : variables explicatives et corrélations inter-évaluateurs.

INTRODUCTION: Objective Structured Clinical Examinations (OSCEs) assess professional performance in a simulated environment. Following their integration into the reform of the 2nd cycle of medical studies (R2C), this pedagogical modality was implemented in France. This study investigates the variability of students' OSCE scores, as well as their inter-rater reproducibility. METHODS: This single-center retrospective study covered several sessions of evaluative OSCE circuits conducted between January 2022 and June 2023. Variables collected were: baseline situation family, competency domain, presence of a standardized participant for stations; gender and professional status for evaluators; scores (global, clinical and communication skills), number of previously completed OSCE circuits and faculty scores for students. RESULTS: The variability of the overall score was explained mainly (79.7%, CI95% [77.4; 82.0]) by the station factor. The student factor and the circuit factor explained 7.5% [12.9; 20.2] and<0.01% [2.10-13; 2.10-9] respectively. The inter-rater intra-class correlation coefficient was 87.2% [86.4; 87.9] for the global score. Station characteristics (starting situation, domain) and evaluator characteristics (gender, status) were significantly associated with score variations. CONCLUSION: This first study on the variability of OSCE circuit scores in France shows good reproducibility with influence of station characteristics. In order to standardize circuits, variability linked to the domain competency should be considered as well.

Stabilisation of femoral capital physeal fractures using transcervical pinning in cats: 19 cases (2014-2022).

OBJECTIVES: To report the short-term clinical and radiographic outcomes in cats with femoral capital physeal fractures stabilised with transcervical pinning. MATERIALS AND METHODS: Medical records of cats diagnosed with femoral capital physeal fractures and treated with transcervical pinning were reviewed. The collected data included signalment, weight, time from lameness to surgery, reported trauma, affected side, concomitant orthopaedic injuries, radiographs, osteoarthritis, femoral neck osteolysis, proximal femoral epiphysis to femoral neck ratio, fracture reduction, implants, complications and clinical evaluation results. An owner questionnaire was used for long-term follow-up. RESULTS: Nineteen cats with a total of 21 fractures met the inclusion criteria. Fifteen of the 19 cats showed no signs of lameness at the 1-month follow-up. Major and catastrophic complications occurred in 9.5% and 23.8% of the fractures, respectively. All catastrophic complications occurred in fractures with a high preoperative osteolysis grade (2 or 3). CLINICAL SIGNIFICANCE: In our study, transcervical pinning was found to be a reliable fixation method for the treatment of femoral capital physeal fractures in cats with minimal preoperative femoral neck osteolysis. High rates of implant failure with loss of fracture reduction were observed in cats with high-grade preoperative osteolysis.

Successful intergeneric transfer of a major apple scab resistance gene (Rvi6) from apple to pear and precise comparison of the downstream molecular mechanisms of this resistance in both species.

BACKGROUND: Scab is the most important fungal disease of apple and pear. Apple (Malus x domestica Borkh.) and European pear (Pyrus communis L.) are genetically related but they are hosts of two different fungal species: Venturia inaequalis for apple and V. pyrina for European pear. The apple/V. inaequalis pathosystem is quite well known, whereas knowledge about the pear/V. pyrina pathosystem is still limited. The aim of our study was to analyse the mode of action of a major resistance gene of apple (Rvi6) in transgenic apple and pear plants interacting with the two scab species (V. inaequalis and V. pyrina), in order to determine the degree of functional transferability between the two pathosystems. RESULTS: Transgenic pear clones constitutively expressing the Rvi6 gene from apple were compared to a scab transgenic apple clone carrying the same construct. After inoculation in greenhouse with V. pyrina, strong defense reactions and very limited sporulation were observed on all transgenic pear clones tested. Microscopic observations revealed frequent aborted conidiophores in the Rvi6 transgenic pear / V. pyrina interaction. The macro- and microscopic observations were very comparable to the Rvi6 apple / V. inaequalis interaction. However, this resistance in pear proved variable according to the strain of V. pyrina, and one of the strains tested overcame the resistance of most of the transgenic pear clones. Comparative transcriptomic analyses of apple and pear resistant interactions with V. inaequalis and V. pyrina, respectively, revealed different cascades of molecular mechanisms downstream of the pathogen recognition by Rvi6 in the two species. Signal transduction was triggered in both species with calcium (and G-proteins in pear) and interconnected hormonal signaling (jasmonic acid in pear, auxins in apple and brassinosteroids in both species), without involvement of salicylic acid. This led to the induction of defense responses such as a remodeling of primary and secondary cell wall, lipids biosynthesis (galactolipids in apple and cutin and cuticular waxes in pear), systemic acquired resistance signal generation (in apple) or perception in distal tissues (in pear), and the biosynthesis of phenylpropanoids (flavonoids in apple but also lignin in pear). CONCLUSION: This study is the first example of a successful intergeneric transfer of a resistance gene among Rosaceae, with a resistance gene functioning towards another species of pathogen.

COVID-19 outpatient management: Shorter time to recovery in Healthcare workers according to an electronic daily symptoms assessment.

OBJECTIVES: Our aim is to compare the course of the disease between healthcare workers (HCWs) and non-HCWs suffering from covid-19 and eligible for outpatient management. METHODS: Single-center prospective cohort of outpatients with covid-19, diagnosed between the 10th March and the 2nd April, 2020 with a daily collection of symptoms by an on-line auto-questionnaire. RESULTS: A total of 186 patients were included (median age, 41 years [interquartile range, 19-78 years]; 74.2% female), of whom 132 (71%) were HCWs. The median follow-up after symptom onset was 14 (min 4-max 24) days. HCWs were significantly younger than non-HCWs (median age 40.3 years vs. 47.2 years [P<0.005]), and 81.8% were women. Four patients (2.2%) were hospitalized including one HCW. The median time to recovery was 9 days after symptom onset (95% CI 8-11) in the global population and respectively 8 (95% CI 8-9) and 13 (95% CI 11-15) days in HCWs and in non-HCWs (P<0.005). After adjusting for age, co-morbidities, and gender, the instantaneous risk ratio for symptom absence in HCWs was 1.76 compared with non-HCWs (95% CI [1.16-2.67], P=0.037). CONCLUSION: HCWs suffering from covid-19 had favorable outcomes and had a shorter time to recovery than non HCWs.

SARS-CoV-2 infection: advocacy for training and social distancing in healthcare settings.

This article reports the observed rate of infection with severe acute respiratory syndrome coronavirus-2 in healthcare workers (HCWs) who worked on wards dedicated to care of patients with coronavirus disease 2019 (COVID-19) compared with HCWs who worked on non-COVID-19 wards. The infection rate was significantly higher among HCWs who worked on non-COVID-19 wards (odds ratio 2.3, P=0.005), illustrating the need to strengthen social distancing measures and training.

Health students' knowledge of sexually transmitted infections and risky behaviors before participation to the health promotion program.

OBJECTIVES: We aimed to evaluate knowledge of health students (HS) enrolled in a health promotion program about sexually transmitted infections (STIs) and the frequency of risky behaviors. METHODS: HS answered two anonymous questionnaires, a mandatory one about knowledge of STIs and STI prevention and an optional one about behaviors. RESULTS: Two-hundred and sixteen HS answered the first questionnaire and 183 answered the second one. Eighty-three percent of HS had a good knowledge of HIV transmission, but half of them were aware of pre-exposure and post-exposure prophylaxes for HIV. The role of HPV infection in genital warts and anal cancer was respectively known by 33 (15.3%) and 10 (4.6%) HS. Thirty-six HS (19.7%) reported having unprotected sex in the previous 12 months. CONCLUSION: French HS had a poor knowledge of STIs and STI prevention, and risky behaviors. It is necessary to provide good training on STIs to HS.

Acute kidney injury in infective endocarditis: A retrospective analysis.

BACKGROUND: Acute kidney injury (AKI) is associated with high case fatality in infective endocarditis (IE), but epidemiological data on the frequency of AKI during IE is scarce. We aimed to describe the frequency and risk factors for AKI during the course of IE using Kidney Disease: Improving Global Outcomes consensual criteria. METHODS: Using the French hospital discharge database (French acronym PMSI), we retrospectively reviewed the charts of 112 patients presenting with a first episode of probable or definite IE between January 2010 and May 2015. RESULTS: Seventy-seven patients (68.8%) developed AKI. In univariate analysis, risk factors for AKI were cardiac surgery for IE (n=29, 37.7% vs. n=4, 1.4%, P<0.0005), cardiac failure (n=29, 36.7% vs. n=1, 2.9%, P<0.0005), diabetes mellitus (n=14, 18.2% vs. n=1, 0.9%, P=0.034), and prosthetic valve IEs (n=24, 31.2% vs. n=4, 11.4%). No differences were observed for gentamicin exposure (n=57, 64% vs. n=32, 86.5%, P=0.286). Prosthetic valve IE, cardiac failure, and vancomycin exposure were independently associated with AKI with respective odds ratio of 5.49 (95% CI 1.92-17.9), 4.37 (95% CI 4.37-465.7), and 1.084 (1.084-16.2). Mean length of hospital stay was significantly longer in patients presenting with AKI than in controls (respectively 52.4±22.1 days vs. 39.6±12.6, P<0.005). CONCLUSION: AKI is very frequent during IE, particularly in patients with prosthetic valve IE, cardiac failure, and those receiving vancomycin.

Impact of amoxicillin and oral amoxicillin-clavulanic acid defined daily doses on consumption indicators.

OBJECTIVE: To measure the impact of the differences between recommended daily average maintenance doses and defined daily doses on antimicrobial consumption indicators (amoxicillin+amoxicillin-clavulanic acid). MATERIAL AND METHODS: We calculated the impact of the antibacterial agent switch or de-escalation and reviewed the consumption indicators of our French hospital with defined daily doses (DDD) of 3g. We also applied these DDDs to French and European community setting indicators in private practice. RESULTS: We observed a modification in trend consumption indicators over a 10-year period: indicator stability for our hospital (-0.32% versus +5.45%), decrease for French community indicators (-9.9% versus +6.7%). The recalculated 2015 data for European community indicators showed France as the 9th largest European consumer (versus 4th position before). CONCLUSION: DDDs must be modified to have appropriate indicators to evaluate antimicrobial stewardship programs and to penalize prescriptions favoring the emergence of resistant pathogens.

Intracellular activity of antimicrobial compounds used for Staphylococcus aureus nasal decolonization.

Background: Staphylococcus aureus is able to invade mammalian cells during infection and was recently observed inside nasal mucosa of healthy carriers. Objectives: To determine the intracellular activity of antimicrobial compounds used for decolonization procedures using a cell model mimicking S. aureus nasal epithelium invasion. Patients and methods: HaCaT cells and human nasal epithelial cells (HNECs) recovered from nasal swabs of S. aureus carriers were visualized by confocal laser scanning microscopy to detect intracellular S. aureus cells. An HaCaT cell model, mimicking S. aureus internalization observed ex vivo in HNECs, was used to assess the intracellular activity against S. aureus of 21 antimicrobial compounds used for nasal decolonization, including mupirocin and chlorhexidine. Results: HaCaT cells and HNECs were found to internalize S. aureus with the same focal pattern. Most antimicrobial compounds tested on HaCaT cells were shown to have weak activity against intracellular S. aureus. Some systemic antimicrobials, including fusidic acid, clindamycin, linezolid, minocycline, ciprofloxacin, moxifloxacin, rifampicin and levofloxacin, reduced S. aureus intracellular loads by 0.43-1.66 log cfu/106 cells compared with the control (P < 0.001). By contrast, mupirocin and chlorhexidine reduced the S. aureus intracellular load by 0.19 and 0.23 log cfu/106 cells, respectively. Conclusions: These data indicate that most of the antimicrobial compounds used for nasal decolonization, including mupirocin and chlorhexidine, exhibit weak activity against intracellular S. aureus using the HaCaT cell model. This work emphasizes the need to better understand the role of the S. aureus intracellular reservoir during nasal colonization in order to improve decolonization procedures.

The French Infectious Diseases Society's readiness and response to epidemic or biological risk-the current situation following the Middle East respiratory syndrome coronavirus and Ebola virus disease alerts.

CONTEXT: In 2012, the French Infectious Diseases Society (French acronym SPILF) initiated the "Coordination of epidemic and biological risk" (SPILF-COREB - Emergences [SCE]) group to support the readiness and response of healthcare workers (HCWs) to new alerts. OBJECTIVE: To present the SCE group, its functioning, and the main support it provided for frontline HCWs. METHODS: A multidisciplinary group of heads of infectious disease departments from reference hospitals was created to build a network of clinical expertise for care, training, and research in the field of epidemic and biological risk (EBR). The network developed a set of standardized operational procedures (SOPs) to guide interventions to manage EBR-suspect patients. RESULTS: A working group created the SOP aimed at frontline HCWs taking care of patients. Priority was given to the development of a generic procedure, which was then adapted according to the current alert. Five key steps were identified and hierarchized: detecting, protecting, caring for, alerting, and referring the EBR patient. The interaction between clinicians and those responsible for the protection of the community was crucial. The SOPs validated by the SPILF and its affiliates were disseminated to a wide range of key stakeholders through various media including workshops and the SPILF's website. CONCLUSION: SPILF can easily adapt and timely mobilize the EBR expertise in case of an alert. The present work suggests that sharing and discussing this experience, initiated at the European level, can generate a new collective expertise and needs to be further developed and strengthened.

Hospital-acquired infections documented by repeated annual prevalence surveys over 15 years.

OBJECTIVE: To estimate the benefits of iterative prevalence surveys in detecting trends of hospital-acquired infections (HAIs). METHODS: On the basis of the French protocol for national prevalence studies, HAI data of 15 consecutive annual surveys performed at the same period by the same group of investigators was gathered in a single database to describe the trend of HAIs in a University Hospital over a 15-year period. RESULTS: A total of 20,401 patients were included. Overall, the prevalence of patients presenting with at least one HAI acquired in our University Hospital was 5.1% [95% CI, 4.8-5.4%]. The prevalence of HAIs and antimicrobial drug use significantly decreased over time (P<0.01). CONCLUSION: Despite limitations, repeated prevalence surveys can be a useful tool for promoting control measures to better prevent HAIs.

Extensively drug-resistant bacteria: Which ethical issues?

OBJECTIVE: The increased bacterial resistance to antibiotics has now become a public health concern. How can we preserve the well-being of patients presenting with infections caused by extensively drug-resistant bacteria (EDRBs) and that of their contacts without inducing any loss of chance of survival, all the while living together and controlling the spread of these EDRBs? METHOD: Terre d'éthique, a French territorial ethics committee, was asked to reflect on this topic by the infection control unit of a French University Hospital as it raises many ethical issues. RESULTS: Patients are at the core of any ethical approach, and respecting their autonomy is fundamental. Patients should be adequately informed to be able to give consent. Indeed, the creation and dissemination of a register (list of names of contacts or infected patients) entails responsibility of the infected person and that of the community. This responsibility leads to an ethical dilemma as protecting the group (the whole population) necessarily means limiting individual freedom. The principle of autonomy should thus be compared with that of solidarity. Is medical confidentiality an obstacle to the sharing of information or lists of names? CONCLUSION: We did not aim to answer our problematic but merely wanted to show the complexity of EDRB spread in a broader societal and economic context, all the while respecting the rights of patients.

Carbapenemase-producing Acinetobacter baumannii: An outbreak report with special highlights on economic burden.

OBJECTIVE: We aimed to describe the management of a carbapenemase-producing Acinetobacter baumannii (CP-AB) outbreak using the Outbreak Reports and Intervention Studies of Nosocomial Infection (ORION) statement. We also aimed to evaluate the cost of the outbreak and simulate costs if a dedicated unit to manage such outbreak had been set-up. METHODS: We performed a prospective epidemiological study. Multiple interventions were implemented including cohorting measures and limitation of admissions. Cost estimation was performed using administrative local data. RESULTS: Five patients were colonized with CP-AB and hospitalized in the neurosurgery ward. The index case was a patient who had been previously hospitalized in Portugal. Four secondary colonized patients were further observed within the unit. The strains of A. baumannii were shown to belong to the same clone and all of them produced an OXA-23 carbapenemase. The closure of the ward associated with the discharge of the five patients in a cohorting area of the Infectious Diseases Unit with dedicated staff put a stop to the outbreak. The estimated cost of this 17-week outbreak was $474,474. If patients had been managed in a dedicated unit - including specific area for cohorting of patients and dedicated staff - at the beginning of the outbreak, the estimated cost would have been $189,046. CONCLUSION: Controlling hospital outbreaks involving multidrug-resistant bacteria requires a rapid cohorting of patients. Using simulation, we highlighted cost gain when using a dedicated cohorting unit strategy for such an outbreak.

Decolonization of Staphylococcus aureus carriage.

Staphylococcus aureus nasal colonization is a well-known independent risk factor for infection caused by this bacterium. Screening and decolonization of carriers have been proven effective in reducing S. aureus infections in some populations. However, a gap remains between what has been proven effective and what is currently done. We aimed to summarize recommendations and current knowledge of S. aureus decolonization to answer the following questions: Why? For whom? How? When? And what are the perspectives?

Vaccine hesitancy among general practitioners: evaluation and comparison of their immunisation practice for themselves, their patients and their children.

To gain knowledge about vaccine hesitancy among general practitioners (GPs), we conducted a survey to compare their vaccination attitudes for themselves, their children and their patients. A questionnaire survey was sent to GPs working in private practice in the Rhône-Alpes region, France, between October 2013 and January 2014. GPs' immunisation practices for diphtheria-tetanus-poliomyelitis (DTP), measles-mumps-rubella (MMR), pneumococcal, pertussis, hepatitis B (hepB), human papillomavirus (HPV), seasonal and H1N1 influenza and meningococcal C (menC) vaccines were considered. Divergence was defined by the presence of at least one different immunisation practice between their patients and their children. A total of 693 GPs answered the questionnaire. When considering all investigated vaccines, 45.7 % of divergence was found. Individually, divergence was highest for the newest and more controversial, i.e. HPV (11.8 %), hepB (13.1 %), menC (23.7 %) and pneumococcal (19.8 %) vaccines. Only 73.9 % of GPs declared that they recommended HPV vaccine for their daughters. After multivariate analysis, older age was associated with higher risk of divergence. According to the French 2012 recommendations, GPs were insufficiently immunised, with 88 % for DTP and 72 % for pertussis. GPs declared to recommend vaccination against DTP, pertussis and MMR for their patients and their children in more than 95 % of cases. The declared rates of recommendation were lower than 90 % for other vaccines. These results bring new insight about vaccine hesitancy. GPs have divergent immunisation attitudes toward their relatives and their patients, especially when considering the newest and most controversial vaccines, with HPV vaccine being the main focus of controversies.

Preventing healthcare-associated infections: Residents and attending physicians need better training in advanced isolation precautions.

OBJECTIVE: Compliance with advanced isolation precautions (IPs) is crucial to reduce healthcare-associated infections. Our aim was to evaluate physician's knowledge and attitudes related to IPs. METHODS: An online questionnaire was sent to our hospital's physicians (attending physicians and residents). RESULTS: A total of 111 physicians completed the questionnaire: 60 (54%) attending physicians and 51 (46%) residents. Overall, respondents had a poor knowledge of the three types of IPs, especially droplet precautions (13 correct answers, 11.7%) and airborne IP (17 correct answers, 16.3%). We observed a statistically significant difference between attending physicians and residents for the type of IP to prescribe to a patient presenting with multidrug-resistant urinary infection: 44 residents (86%) gave the correct answer vs 42 attending physicians (70%), P=0.04. Physicians (both residents and attending physicians) who were already familiar with the dedicated webpage available on the hospital's intranet (n=40) obtained a score of 4.75/10 (±2.0) compared with 4.03/10 (±1.7) for those who had never used that tool (n=71). The difference was statistically significant (P=0.04). The average score for both residents and attending physicians was 4.3/10 (±1.9, range: 1-10). Attending physicians' and residents' scores were 4/10 (±1.8) and 4.5/10 (±1.9), respectively, but the difference was not statistically significant (P=0.14). CONCLUSION: Physicians' knowledge of IPs was insufficient. Improvement in medical training is needed. The use of a dedicated webpage on hospitals' intranet could help physicians acquire better knowledge on that matter.

Contamination of healthcare workers' mobile phones by epidemic viruses.

Mobile phones (MPs) are potential reservoirs of nosocomial bacteria, but few data are available concerning viruses. We aimed to evaluate the presence of virus RNA from epidemic viruses including metapneumovirus, respiratory syncytial virus, influenza viruses, rotavirus (RV) and norovirus on the MPs used by healthcare workers (HCWs) and to relate it to hygiene measures. An anonymous behavioural questionnaire about MP use at hospital was administered to the HCWs of four adult and paediatric departments of a university hospital. After sampling personal (PMP) and/or professional MPs (digital enhanced cordless telephone, DECT), virus RNAs were extracted and amplified by one-step real-time reverse transcription-quantitative PCR. The molecular results were analysed in a masked manner in relation to the behavioural survey. Questionnaires from 114 HCWs (25 [corrected] senior physicians, 30 residents, 32 nurses, 27 nurses' assistants) working either in adult (n = 58) or paediatric (n = 56) departments were analysed. Medical personnel used their PMP more frequently than paramedical HCWs (33/65 vs. 10/59, p <0.001). MPs were used during care more frequently in adult wards than in paediatric ones (46/58 vs. 27/56, p <0.001). Virus RNA was detected on 42/109 (38.5%) collected MPs, with RV found on 39, respiratory syncytial virus on three and metapneumovirus on one. The presence of virus RNA was significantly associated with MPs from the paediatric HCWs (p <0.001). MPs routinely used in hospital, even during care, can host virus RNA, especially RV. Promotion of frequent hand hygiene before and after MP use, along with frequent cleaning of MPs, should be encouraged.

French recommendations for the prevention of 'emerging extensively drug-resistant bacteria' (eXDR) cross-transmission.

Controlling the spread of multi- or extensively drug-resistant bacteria (MDR or XDR) includes a dual strategy for reducing antibiotic prescriptions and preventing their spread from patient carriers. Standard precautions are applicable to all health professionals caring for any patients; additional barrier precautions (isolation) are recommended for patients carrying transmissible infectious diseases or MDR bacteria in sporadic or epidemic situations. Moreover, additional precautions may be required for populations at particular risk of infection or colonization by emerging XDR (eXDR), defined in our country as carbapenemase-producing Enterobacteriaceae and vancomycin-resistant enterococci. Our ability to detect and identify eXDR carriers early and ensure their follow-up, through effective communication between all those involved, is a significant challenge for controlling their spread. Thus, the French High Committee for Public Health has updated and standardized all French existing recommendations concerning the prevention of the cross-transmission of these bacteria, and these recommendations are summarized in this review. The recommendations are based on scientific and operational knowledge up to 2013. Different preventive strategies are recommended for patients found to be carrying eXDR and those who are considered to be at risk of having eXDR because of a history of contact. The local context, the experience of the infection control team, the different times at which detection of eXDR takes place (during admission, hospitalization, etc.) and the epidemiological situation (sporadic cases, clusters, outbreaks, widespread epidemic) must be included in risk assessments that in turn inform the control measures that should be applied in each clinical circumstance.

Control of emerging extensively drug-resistant organisms (eXDRO) in France: a survey among infection preventionists from 286 healthcare facilities.

We performed a multicenter survey in May-June 2012 to assess strategies in preventing the spread of emerging extensively drug-resistant organisms (eXDRO), including glycopeptide-resistant enterococci and carbapenemase-producing Enterobacteriaceae, in a convenient sample of French healthcare facilities (HCFs). The collected data included organization and measures to: (1) identify patients at risk for carrying eXDRO, (2) investigate and control sporadic cases or outbreaks, and (3) describe prior 2010-2012 episodes with one or more colonized patients. Of the 286 participating HCFs, 163 (57 %) and 134 (47 %) reported having a specific procedure to detect repatriates or patients hospitalized in foreign countries within the last year, respectively. Among the 97 HCFs with prior at-risk patient management experience, contact precautions, hospitalization in a single room, and screening for eXDRO carriage were quasi-systematically performed (n = 92/97, 95 %). The alleged time between admission and alert ranged from 24 to 48 h after the patient's admission; 203 (71 %) HCFs recommended obtaining three successive negative screening samples to declare a patient free of eXDRO colonization. During the last two years, 64 HCFs (23 %) had to manage at least one eXDRO case, with a total of 20 outbreaks with more than one secondary case. This first national survey shows that French HCFs were not totally ready to control eXDRO spread in 2012. Their previous experiences and capacities in controlling eXDRO outbreaks are quite heterogeneous from one hospital to another. Further researches are needed in order to understand the constraints in applying national guidance.