Challenges of parenting children born before 24 weeks of gestation.

AIM: To assess experience of care, well-being of parents and children's development in a cohort of extremely premature infants born <24 weeks of gestation in Sweden from 2007 to 2018. METHODS: A survey based on multiple questionnaires answered by 124/349 (35.5%) parents. RESULTS: The median age of parents and children was 43 and 9 years, respectively; 74.2% were mothers. Parents expressed high healthcare satisfaction. Following discharge from neonatal care, the satisfaction with the infant's treatment, support from personnel and being respected as a parent significantly declined but remained high. The criteria for suspected developmental deviation according to the screening test early symptomatic syndromes eliciting neurodevelopmental clinical examinations-questionnaire was fulfilled by 84.3%, 55.6% had suspected avoidant restrictive food intake disorder and 47.9% had visual perception problems. Parents experienced severe fatigue (48.6%) despite strong social support and family self-efficacy. Economic support was provided to 30.6%, and 37.9% of children were enrolled in habilitation services. CONCLUSION: This study highlighted the substantial challenges faced by parents of infants born before 24 weeks of gestation, including decreased satisfaction post-discharge, fatigue and concerns about children's well-being. The findings underscore the need for comprehensive family-centred support and long-term multi-professional follow-up centres.

FGF21 via mitochondrial lipid oxidation promotes physiological vascularization in a mouse model of Phase I ROP.

Hyperglycemia in early postnatal life of preterm infants with incompletely vascularized retinas is associated with increased risk of potentially blinding neovascular retinopathy of prematurity (ROP). Neovascular ROP (Phase II ROP) is a compensatory but ultimately pathological response to the suppression of physiological postnatal retinal vascular development (Phase I ROP). Hyperglycemia in neonatal mice which suppresses physiological retinal vascular growth is associated with decreased expression of systemic and retinal fibroblast growth factor 21 (FGF21). FGF21 administration promoted and FGF21 deficiency suppressed the physiological retinal vessel growth. FGF21 increased serum adiponectin (APN) levels and loss of APN abolished FGF21 promotion of physiological retinal vascular development. Blocking mitochondrial fatty acid oxidation also abolished FGF21 protection against delayed physiological retinal vessel growth. Clinically, preterm infants developing severe neovascular ROP (versus non-severe ROP) had a lower total lipid intake with more parenteral and less enteral during the first 4 weeks of life. Our data suggest that increasing FGF21 levels in the presence of adequate enteral lipids may help prevent Phase I retinopathy (and therefore prevent neovascular disease).

Clinical prediction of laboratory-confirmed influenza in adults with influenza-like illness in primary care. A randomized controlled trial secondary analysis in 15 European countries.

BACKGROUND: Clinical findings do not accurately predict laboratory diagnosis of influenza. Early identification of influenza is considered useful for proper management decisions in primary care. OBJECTIVE: We evaluated the diagnostic value of the presence and the severity of symptoms for the diagnosis of laboratory-confirmed influenza infection among adults presenting with influenza-like illness (ILI) in primary care. METHODS: Secondary analysis of patients with ILI who participated in a clinical trial from 2015 to 2018 in 15 European countries. Patients rated signs and symptoms as absent, minor, moderate, or major problem. A nasopharyngeal swab was taken for microbiological identification of influenza and other microorganisms. Models were generated considering (i) the presence of individual symptoms and (ii) the severity rating of symptoms. RESULTS: A total of 2,639 patients aged 18 or older were included in the analysis. The mean age was 41.8 ± 14.7 years, and 1,099 were men (42.1%). Influenza was microbiologically confirmed in 1,337 patients (51.1%). The area under the curve (AUC) of the model for the presence of any of seven symptoms for detecting influenza was 0.66 (95% confidence interval [CI]: 0.65-0.68), whereas the AUC of the symptom severity model, which included eight variables-cough, fever, muscle aches, sweating and/or chills, moderate to severe overall disease, age, abdominal pain, and sore throat-was 0.70 (95% CI: 0.69-0.72). CONCLUSION: Clinical prediction of microbiologically confirmed influenza in adults with ILI is slightly more accurate when based on patient reported symptom severity than when based on the presence or absence of symptoms.

Influenza is usually diagnosed clinically. However, the accuracy of a diagnosis of influenza based on clinical features is limited because symptoms overlap considerably with those caused by other microorganisms. This study examined whether identification of the severity rather than the presence of key signs and symptoms could aid in the diagnosis of influenza, thereby helping clinicians to determine when antiviral agent use is appropriate. The authors used the database of a previous randomized clinical trial on the effectiveness of an antiviral carried out in primary care centers in 15 countries in Europe during three epidemic periods from 2015/2016 to 2017/2018. Participants with influenza symptoms were included and they were asked about the presence and severity of different symptoms during the baseline visit with their doctors and a nasopharyngeal swab was taken for microbiological analysis. Overall, only 51% of the patients aged 18 or older had a confirmed influenza infection. Clinical findings are not particularly useful for confirming or excluding the diagnosis of influenza. However, the results of our study recommend considering how intense the different symptoms are, since key symptoms rated as moderate or severe are slightly better for predicting flu rather than the presence or absence of these symptoms.

Association of platelet deficiency with severe retinopathy of prematurity: a review.

AIM: The aim of this review was to compile existing evidence on the role of platelets in the development of severe retinopathy of prematurity (ROP), highlight the strengths and weaknesses of the available studies and critically discuss the reported data. METHODS: A comprehensive literature search was conducted on PubMed from January 2000 to January 2022, and the reference lists of the included studies were screened manually. RESULTS: There were 19 primary studies that fulfilled the eligibility criteria. Experimental research indicated lower platelet count in mice oxygen-induced retinopathy model compared with normoxia controls, while platelet transfusions suppressed neovascularisation. The latter finding was not consistently confirmed in clinical research, where a low platelet count, an increased number of thrombopenic episodes and of platelet transfusions have all been implicated in the development of ROP requiring treatment, either type I or aggressive posterior or both. However, existing studies exhibit significant clinical heterogeneity and present methodological limitations that imperil their reliability and validity. CONCLUSION: Platelet deficiency has been associated with severe ROP. However, critical thresholds of platelet parameters are still unrecognised. Future research is required to determine whether platelet parameters can be predictive biomarkers for ROP requiring treatment and at what thresholds.

Neurodevelopmental disorders and somatic diagnoses in a national cohort of children born before 24 weeks of gestation.

AIM: This study investigated childhood diagnoses in children born extremely preterm before 24 weeks of gestation. METHODS: Diagnoses of neurodevelopmental disorders and selected somatic diagnoses were retrospectively retrieved from national Swedish registries for children born before 24 weeks from 2007 to 2018. Their individual medical files were also examined. RESULTS: We studied 383 children born at a median of 23.3 (range 21.9-23.9) weeks, with a median birthweight of 565 (range 340-874) grams. Three-quarters (75%) had neurodevelopmental disorders, including speech disorders (52%), intellectual disabilities (40%), attention deficit hyperactivity disorder (30%), autism spectrum disorders (24%), visual impairment (22%), cerebral palsy (17%), epilepsy (10%) and hearing impairment (5%). More boys than girls born at 23 weeks had intellectual disabilities (45% vs. 27%, p < 0.01) and visual impairment (25% vs. 14%, p < 0.01). Just over half of the cohort (55%) received habilitation care. The majority (88%) had somatic diagnoses, including asthma (63%) and failure to thrive/short stature (39%). CONCLUSION: Most children born before 24 weeks had neurodevelopmental disorders and/or additional somatic diagnoses in childhood and were referred to habilitation services. Clinicians should be aware of the multiple health and developmental problems affecting these children. Resources are needed to identify their long-term support needs at an early stage.

National cohort of infants born before 24 gestational weeks showed increased survival rates but no improvement in neonatal morbidity.

AIM: To describe survival and neonatal morbidities in infants born before 24 weeks of gestation during a 12-year period. METHODS: Data were retrieved from national registries and validated in medical files of infants born before 24 weeks of gestation 2007-2018 in Sweden. Temporal changes were evaluated. RESULTS: In 2007-2018, 282 live births were recorded at 22 weeks and 460 at 23 weeks of gestation. Survival to discharge from hospital of infants born alive at 22 and 23 weeks increased from 20% to 38% (p = 0.006) and from 45% to 67% (p < 0.001) respectively. Caesarean section increased from 12% to 22% (p = 0.038) for infants born at 22 weeks. Neonatal morbidity rates in infants alive at 40 weeks of postmenstrual age (n = 399) were unchanged except for an increase in necrotising enterocolitis from 0 to 33% (p = 0.017) in infants born at 22 weeks of gestation. Bronchopulmonary dysplasia was more common in boys than girls, 90% versus 82% (p = 0.044). The number of infants surviving to 40 weeks doubled over time. CONCLUSION: Increased survival of infants born before 24 weeks of gestation resulted in increasing numbers of very immature infants with severe neonatal morbidities likely to have a negative impact on long-term outcome.

Challenges and opportunities for general practice specific CME in Europe - a narrative review of seven countries.

BACKGROUND: Several changes have led to general practitioners (GPs) working in a more differentiated setting today and being supported by other health professions. As practice changes, primary care specific continuing medical education (CME) may also need to adapt. By comparing different primary care specific CME approaches for GPs across Europe, we aim at identifying challenges and opportunities for future development. METHODS: Narrative review assessing, analysing and comparing CME programs for general practitioners across different north-western European countries (UK, Norway, the Netherlands, Belgium (Flanders), Germany, Switzerland, and France). Templates containing detailed items across seven dimensions of country-specific CME were developed and used. These dimensions are role of primary care within the health system, legal regulations regarding CME, published aims of CME, actual content of CME, operationalisation, funding and sponsorship, and evaluation. RESULTS: General practice specific CME in the countries under consideration are presented and comparatively analysed based on the dimensions defined in advance. This shows that each of the countries examined has different strengths and weaknesses. A clear pioneer cannot be identified. Nevertheless, numerous impulses for optimising future GP training systems can be derived from the examples presented. CONCLUSIONS: Independent of country specific CME programs several fields of potential action were identified: the development of curriculum objectives for GPs, the promotion of innovative teaching and learning formats, the use of synergies in specialist GP training and CME, the creation of accessible yet comprehensive learning platforms, the establishment of clear rules for sponsorship, the development of new financing models, the promotion of fair competition between CME providers, and scientifically based evaluation.

Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial.

BACKGROUND: Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with influenza-like illness reduces time to recovery overall and in key subgroups. METHODS: We did an open-label, pragmatic, adaptive, randomised controlled trial of adding oseltamivir to usual care in patients aged 1 year and older presenting with influenza-like illness in primary care. The primary endpoint was time to recovery, defined as return to usual activities, with fever, headache, and muscle ache minor or absent. The trial was designed and powered to assess oseltamivir benefit overall and in 36 prespecified subgroups defined by age, comorbidity, previous symptom duration, and symptom severity, using a Bayesian piece-wise exponential primary analysis model. The trial is registered with the ISRCTN Registry, number ISRCTN 27908921. FINDINGS: Between Jan 15, 2016, and April 12, 2018, we recruited 3266 participants in 15 European countries during three seasonal influenza seasons, allocated 1629 to usual care plus oseltamivir and 1637 to usual care, and ascertained the primary outcome in 1533 (94%) and 1526 (93%). 1590 (52%) of 3059 participants had PCR-confirmed influenza infection. Time to recovery was shorter in participants randomly assigned to oseltamivir (hazard ratio 1·29, 95% Bayesian credible interval [BCrI] 1·20-1·39) overall and in 30 of the 36 prespecified subgroups, with estimated hazard ratios ranging from 1·13 to 1·72. The estimated absolute mean benefit from oseltamivir was 1·02 days (95% [BCrI] 0·74-1·31) overall, and in the prespecified subgroups, ranged from 0·70 (95% BCrI 0·30-1·20) in patients younger than 12 years, with less severe symptoms, no comorbidities, and shorter previous illness duration to 3·20 (95% BCrI 1·00-5·50) in patients aged 65 years or older who had more severe illness, comorbidities, and longer previous illness duration. Regarding harms, an increased burden of vomiting or nausea was observed in the oseltamivir group. INTERPRETATION: Primary care patients with influenza-like illness treated with oseltamivir recovered one day sooner on average than those managed by usual care alone. Older, sicker patients with comorbidities and longer previous symptom duration recovered 2-3 days sooner. FUNDING: European Commission's Seventh Framework Programme.

Unpasteurised maternal breast milk is positively associated with growth outcomes in extremely preterm infants.

AIM: Extrauterine growth restriction is common among extremely preterm infants. We explored whether intake of unpasteurised maternal milk (MM) and pasteurised donor milk (DM) was associated with longitudinal growth outcomes and neonatal morbidities in extremely preterm infants. METHODS: Observational study of 90 preterm infants born between 2013 and 2015 in Gothenburg, Sweden. Data were prospectively collected on nutritional and breast milk intakes during the first 28 days. RESULTS: Ninety infants (39 girls and 51 boys) with a median gestational age of 25.3 (22.7-27.9) weeks were evaluated. MM intake (mL/kg/d) correlated positively with almost all z-scores for weight, length and head circumference at 28 postnatal days and at postmenstrual age (PMA) 32 and 36 weeks. After multivariable adjustment, MM intake and weight z-score at 28 postnatal days and at PMA 32 and 36 weeks remained significantly associated. Infants consuming ≥80% MM had more favourable weight z-scores at PMA 32 and 36 weeks. Intake of DM did not correlate with any growth outcomes. Infants without retinopathy of prematurity had a significantly higher intake of MM (mL/kg/d). CONCLUSION: Unpasteurised MM was positively associated with longitudinal growth outcomes. Motivating mothers to provide their infants with their own milk after preterm birth should be emphasised.

Erythropoietin serum levels, versus anaemia as risk factors for severe retinopathy of prematurity.

BACKGROUND: Preterm infants with anaemia are treated with recombinant human erythropoietin (rhEPO). It is debated whether rhEPO treatment is a risk factor for retinopathy of prematurity (ROP). We evaluated longitudinal EPO and haemoglobin levels, blood transfusions and neonatal morbidities as risk factors for severe ROP. METHOD: This prospective study included 78 Swedish infants, born <28 weeks gestational age (GA), screened for ROP. We tested serum EPO levels on postnatal days 1, 7, 14 and 28 and at postmenstrual ages 32, 36 and 40 weeks. Haemoglobin levels and blood transfusions were recorded during postnatal weeks 1-4. Anaemia was defined as haemoglobin ≤110 g/L. RESULTS: During postnatal week 1, infants with severe ROP requiring treatment (28%) more frequently developed anaemia (42.9% versus 8.0%, P = 0.003) and had higher mean EPO levels (postnatal day 7: 14.2 versus 10.8 mIU/mL, P = 0.003) compared to infants with no or less severe ROP not requiring treatment. In multivariable analyses, GA and anaemia during week 1 remained significant risk factors, but elevated EPO level postnatal day 7 was no longer significant. CONCLUSIONS: Among infants born <28 weeks GA, anaemia during week 1 was a significant risk factor for severe ROP requiring treatment but not elevated EPO levels.

Health outcomes of the July 14, 2016 Nice terror attack among hospital-based professionals and students: the « ECHOS de Nice ¼ health survey protocol.

BACKGROUND: The terror attack of July 14, 2016, in Nice, France, resulted in 86 deaths, including children, and several hundred wounded, with a major psychological impact on the population. Hospital staff had to cope with exceptional circumstances which made them vulnerable to detrimental effects on their own health. This paper describes the method that was selected for the survey entitled "ECHOS de Nice 14 Juillet" which aimed to assess the impact of the attack on the psychological, psycho-traumatic and somatic health condition of the Nice University and Lenval hospital staff who were directly or indirectly exposed to the attack, and also to describe the support and care facilities they were offered. METHOD: ECHOS de Nice 14 juillet is an observational, cross-sectional, multicentre study focusing on all the hospital staff and students of both institutions, i.e. 10,100 persons in June 2017. A web-based questionnaire based on the model developed by Santé Publique France (IMPACTS and ESPA 13 novembre 2015) was adapted to the contexts of the healthcare professionals and students employed in these healthcare institutions in Nice and published on line from June 21 to October 30, 2017. The paper describes the tools that were used to meet the aims of the study, i.e. identification of exposure categories ('civilian' exposure for those present during the attack and/or 'professional' exposure); indicators of psychological impact (anxiety, depression, burnout, compassion fatigue, suicidal states, tobacco and alcohol use, self-medications), psycho-traumatic and somatic impact; professional and social impact. Lastly, awareness of availability and use of psychological support and care-follow-up facilities by professionals were investigated. Respondents could include extensive qualitative comments on the various themes explored in the questionnaire, with text analysis complementing that of quantitative data. DISCUSSION: The benefits and limitations of the selected methodology are discussed, in view of contributing useful information to help anticipate and manage health issues among hospital staff who have been victims of traumatic events.

Implementing higher oxygen saturation targets reduced the impact of poor weight gain as a predictor for retinopathy of prematurity.

AIM: This study evaluated poor weight gain as a risk factor for infants who required treatment for retinopathy of prematurity (ROP), by comparing those born before and after the implementation of higher oxygen saturation (SpO2 ) targets at the Queen Silvia Children's Hospital, Gothenburg, Sweden. METHODS: We compared infants born at less than 31 weeks, who were screened and, or, treated for ROP: 127 in 2011-2012 when SpO2 targets were 88-92% and 142 in 2015-2016 when they were 91-95%. The subjects were reviewed for birth characteristics, weekly weight and ROP treatment. Data were analysed using the weight, insulin-like growth factor 1, neonatal, ROP (WINROP) prediction tool. RESULTS: The 2011-2012 infants who needed ROP treatment (12.6%) had significantly poorer postnatal weight gain than those who did not, but this was not seen in the treated (17.6%) and nontreated ROP groups in 2015-2016. WINROP sensitivity decreased from 87.5% in 2011-12 to 48% in 2015-2016. CONCLUSION: After the SpO2 target range was increased from 88-92% to 91-95%, postnatal weight gain was no longer a significant risk factor and WINROP lost its ability to predict ROP requiring treatment. Risk factors clearly change as neonatal care develops.

Extreme prematurity, treated retinopathy, bronchopulmonary dysplasia and cerebral palsy are significant risk factors for ophthalmological abnormalities at 6.5 years of age.

AIM: This study evaluated the contributions of various prenatal and postnatal predictive factors to a documented high prevalence of ophthalmological abnormalities in children aged 6.5 years who were born extremely preterm. METHODS: We carried out a prospective population-based study of all children born in Sweden at a gestational age of 22 + 0 to 26 + 6 weeks based on the Extremely Preterm Infants in Sweden Study. The main outcome measures were a combined score of visual impairment, refractive errors and strabismus at 6.5 years of age. Models of univariate and multivariable regression were used to analyse potential prenatal and postnatal predictive factors at different clinically relevant time-points from one minute after birth to 30 months. RESULTS: We focused on 399 known extremely preterm survivors and compared them to 300 full-term controls. Significant antecedents for ophthalmological abnormalities included prematurity per se, retinopathy of prematurity that required treatment, severe bronchopulmonary dysplasia and cerebral palsy. Severe intraventricular haemorrhage was no longer a significant risk factor when we adjusted it for the 30-month cognitive and neuromotor development outcomes. CONCLUSION: This time-course risk analysis model showed a changing panorama of significant risk factors for ophthalmological abnormalities in children aged 6.5 years who were born extremely preterm.

Duration of anaemia during the first week of life is an independent risk factor for retinopathy of prematurity.

AIM: This study evaluated the correlation between retinopathy of prematurity (ROP), anaemia and blood transfusions in extremely preterm infants. METHODS: We included 227 infants born below 28 weeks of gestation at King Edward Memorial Hospital, Perth, Australia, from 2014-2016. Birth characteristics and risk factors for ROP were retrieved, and anaemia and severe anaemia were defined as a haemoglobins of <110 g/L and <80 g/L, respectively. Logistic regression was used for the analysis. RESULTS: Retinopathy of prematurity treatment was needed in 11% of cases and the mean number of blood transfusions (p < 0.01), and mean number of weeks of anaemia (p < 0.001) and of severe anaemia (p < 0.05), had positive associations with ROP cases warranting treatment. In the multivariate logistic regression analysis, the best-fit model of risk factors included anaemic days during first week of life, with an odds ratio (OR) of 1.46% and 95% confidence interval (CI) of 1.16-1.83 (p < 0.05), sepsis during the first 4 weeks of life (OR 3.14, 95% CI 1.10-9.00, p < 0.05) and days of ventilation (OR 1.03, 95% CI 1.01-1.06, p < 0.05). CONCLUSION: The duration of anaemia during the first week of life was an independent risk factor for ROP warranting treatment and preventing early anaemia may decrease this risk.

[How to raise awareness about antibiotics and vaccination among French teenagers?] / Antibiotiques et vaccinations : comment sensibiliser les adolescents français ?

Introduction: Bacterial resistance to antibiotics is a growing concern in Europe, vaccination coverage is inadequate, and young adults, who are the highest antibiotic consumers, have the lowest level of knowledge. Extension of the e-Bug project, a European educational school programme concerning microbes, antibiotics and vaccination, to 15-18-year-olds implies the development of educational resources based on social marketing to promote sustainable behavioural changes. The objectives of the present study, which is part of the needs assessment in France, are to explore the attitudes, knowledge and behaviour of 15-18-year-olds concerning antibiotics and vaccination and their health education needs. Methods: Individual semi-structured interviews were conducted using purposeful sampling of 15- to 18-year-olds, until data saturation, and were transcribed and analysed. Results: The results confirm that teenagers are high antibiotic consumers with poor knowledge. They are interested in their health, but less so in antibiotics and vaccination. Health information is mainly obtained from the Internet, but tends to be criticised. General practitioners play an important role in terms of health information and are also influenced by peers and family. Teenagers believe school should play an important role in health education, which they would prefer to be more interactive: debates, case-stories, sharing experience with peers, parents and health professionals, based on relevant concrete examples, via new technologies. Conclusion: Knowledge gaps revealed among young people during this survey confirm that this age-group should be targeted by a specifically tailored approach. Responders are receptive to information provided by reliable and easily accessible sources. High schools, as well as general practitioners, play an important role in health education in general for this age-group and particularly concerning antibiotics and vaccinations. The Internet is a relevant medium for disseminating information. Teaching should be interactive and take social influences (peers, family) into account.

[Promoting primary care screening for Chlamydia trachomatis infection]. / Promotion du dépistage d'infection à Chlamydia trachomatis en soins primaires.

Background: Lower urogenital tract Chlamydia trachomatis (Ct) infection is the most common bacterial sexually transmitted infection in Europe, especially among young people with multiple partners. Often asymptomatic, its spread and severity are due to delayed diagnosis, highlighting the need for early detection.Objective: Implementation and evaluation of a complex intervention targeting GPs in the Alpes-Maritimes (06) promoting opportunistic screening of Ct infection in young patients.Method: Academic detailing visits provided 105 randomized GPs with tools and patient self-testing kits to include 10 patients over a 6-month period followed by a quantitative (prescribed screenings / reimbursed screenings among visited GPs and all GPs in the Alpes-Maritimes compared to the previous year) and a qualitative assessment (post-interventional interviews with GPs and trainers).Results: In the context of a global increase in screening between the 2013 and 2014 seasons (+15%), the intervention resulted in a significantly higher rate (73%), p = 0.02. Screening was performed in 73 (48%) patients and 12 were PCR-positive. Qualitative analysis of post-interventional interviews with GPs and a focus group of AD visitors highlighted facilitating factors and obstacles to screening. Conclusion: Our intervention, appreciated by the visited GPs, demonstrates its potential impact and feasibility in primary care. GPs used facilitating factors to overcome the identified obstacles. To sustain this intervention, evaluated tools will be available on line to help GPs promote Ct screening as well as for sexual health training targeting GPs.

Identification of cultural determinants of antibiotic use cited in primary care in Europe: a mixed research synthesis study of integrated design "Culture is all around us".

BACKGROUND: Inappropriate antibiotic prescribing, particularly for respiratory tract infections (RTI) in ambulatory care, has become a worldwide public health threat due to resulting antibiotic resistance. In spite of various interventions and campaigns, wide variations in antibiotic use persist between European countries. Cultural determinants are often referred to as a potential cause, but are rarely defined. To our knowledge, so far no systematic literature review has focused on cultural determinants of antibiotic use. The aim of this study was to identify cultural determinants, on a country-specific level in ambulatory care in Europe, and to describe the influence of culture on antibiotic use, using a framework of cultural dimensions. METHOD: A computer-based systematic literature review was conducted by two research teams, in France and in Norway. Eligible publications included studies exploring antibiotic use in primary care in at least two European countries based on primary study results, featuring a description of cultural determinants, and published between 1997 and 2015. Quality assessment was conducted independently by two researchers, one in each team, using appropriate checklists according to study design. Each included paper was characterized according to method, countries involved, sampling and main results, and cultural determinants mentioned in each selected paper were extracted, described and categorized. Finally, the influence of Hofstede's cultural dimensions associated with antibiotic consumption within a primary care setting was described. RESULTS: Among 24 eligible papers, 11 were rejected according to exclusion criteria. Overall, 13 papers meeting the quality assessment criteria were included, of which 11 used quantitative methods and two qualitative or mixed methods. The study participants were patients (nine studies) and general practitioners (two studies). This literature review identified various cultural determinants either patient-related (illness perception/behaviour, health-seeking behaviour, previous experience, antibiotic awareness, drug perception, diagnosis labelling, work ethos, perception of practitioner) or practitioner-related (RTI management, initial training, antibiotic awareness, legal issues, practice context) or both (antibiotic awareness). DISCUSSION AND CONCLUSION: Cultural factors should be considered as exerting an ubiquitous influence on all the consecutive stages of the disease process and seem closely linked to education. Interactions between determinant categories, cultural dimensions and antibiotic use in primary care are multiple, complex and require further investigation within overlapping disciplines. The context of European projects seems particularly relevant.

Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity.

Pathological neovascularization in retinopathy of prematurity (ROP) can cause visual impairment in preterm infants. Current ROP treatments which are not preventative and only address late neovascular ROP, are costly and can lead to severe complications. We showed that topical 0.1% dexamethasone eye drops administered prior to peak neovessel formation prevented neovascularization in five extremely preterm infants at high risk for ROP and suppressed neovascularization by 30% in mouse oxygen-induced retinopathy (OIR) modeling ROP. In contrast, in OIR, topical dexamethasone treatment before any neovessel formation had limited efficacy in preventing later neovascularization, while treatment after peak neovessel formation had a non-statistically significant trend to exacerbating disease. Optimally timed topical dexamethasone suppression of neovascularization in OIR was associated with increased retinal mitochondrial gene expression and decreased inflammatory marker expression, predominantly found in immune cells. Blocking mitochondrial ATP synthetase reversed the inhibitory effect of dexamethasone on neovascularization in OIR. This study provides new insights into topical steroid effects in retinal neovascularization and into mitochondrial function in phase II ROP, and suggests a simple clinical approach to prevent severe ROP.