SEICAV), the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) and the Biomedical Research Centre Network for Respiratory Diseases (CIBERES). These three entities have brought together a multidisciplinary group of experts that includes anaesthesiologists, cardiac and cardiothoracic surgeons, clinical microbiologists, infectious diseases and intensive care specialists, internal medicine doctors and radiologists. Despite the clinical and economic consequences of sternal wound infections, to date, there are no specific guidelines for the prevention, diagnosis and management of mediastinitis based on a multidisciplinary consensus. The purpose of the present document is to provide evidence-based guidance on the most effective diagnosis and management of patients who have experienced or are at risk of developing a post-surgical mediastinitis infection in order to optimise patient outcomes and the process of care. The intended users of the document are health care providers who help patients make decisions regarding their treatment, aiming to optimise the benefits and minimise any harm as well as the workload.This is a consensus document of the Spanish Society of Cardiovascular Infections ( Post-surgical mediastinitis (PSM) after cardiac surgery (CS) is defined as a deep sternal wound infection (SWI) with sternal osteomyelitis with or without infected retrosternal space and is associated high morbidity and mortality . The incThere is little information on the best prevention, diagnosis and management of PSM and it is scattered in the literature. Furthermore, current clinical practices are not always well supported by the medical literature. A critical review of the available information is essential, aiming to provide the best guidance to those interested and committed to this pathology, particularly when, up to now, there is no consensus document by any Spanish scientific society.SEICAV), the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) and the Biomedical Research Centre Network for Respiratory Diseases (CIBERES). These three entities have brought together a multidisciplinary group of experts that includes anaesthesiologists, cardiac and cardiothoracic surgeons, clinical microbiology, infectious diseases and intensive care specialists, internal medicine doctors and radiologists. Despite the clinical and economic consequences of sternal wound infections, to date, there are no specific guidelines for the prevention, diagnosis and management of PSM based on a multidisciplinary consensus. The purpose of the present document is to provide evidence-based guidance on the most effective diagnosis and management of patients who have experienced or are at risk of developing a mediastinitis in order to optimise patient outcomes and the process of care.This is a consensus document of the Spanish Society of Cardiovascular Infections  framework. Each question was assigned to a pair of independent reviewers, who were asked to conduct a systematic search of the medical literature, using the following search strategy: the Cochrane Plus Library (UK), Medline/PUBMED , EMBASE , Scopus (Elsevier) and the Trip database (UK) in the period between 1970 and June 2021. The results of the searches were thoroughly reviewed by panellists, after which a selection and evaluation of relevant articles was carried out. Evidence summaries for each question were prepared by the panel members using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) format was used to write the recommendations and/or to grade the strength of the recommendations . EvidencReviewers were asked to rate the findings in the literature based on the level of evidence extracted from the articles and classify the recommendations by grade of evidence. The National Institute for Health and Care Excellence (NICE) method—an adaptation of the Scottish Intercollegiate Guidelines Network (SIGN)  for inteTo assess the risk of bias, ++, + and − were used to indicate to which extent the key criteria were linked to the potential risk .research needs were contemplated for recommendations when the panellists considered that the need was particularly acute. There is a lack of high quality of evidence for many of the recommendations. Strong recommendations have sometimes been made in the setting of low quality of evidence, when it was believed that most individuals would want the recommended course of action and that most well-informed physicians would agree, despite the low quality of the evidence.There is an ongoing need for research on almost every topic considered in this guideline. However, recommend and suggest indicate strong or weak recommendations, respectively.Recommendations were classified as either “strong” or “weak”  considering the GRADE approach  Table 2Table 2. SEICAV 2019 assembly meeting participants. Prior to its final approval, the document was made available to all members of the Scientific Committee for further information and comments. All panel members took part in the preparation of the guideline and approved the final recommendations. The definitive version was reviewed and submitted to the SEICAV domain for further input and application.The draft of the document was prepared by the coordinator of the scientific committee using the information received from the work groups and suggestions of the The document was structured in four different sections: Prevention, Diagnosis, Surgical Management and Medical Management. A summary table has been added at the end of the document.Optimising preoperative glycaemic control is recommended in diabetic patients with high preoperative HbA1c levels (>6.5–7%) to reduce the risk of mediastinitis.Evidence level 2++. Strong recommendation, moderate quality of evidence.Perioperative hyperglycaemia has been shown to be associated with an increased risk of major adverse events following cardiac surgery, particularly in cases of deep surgical wound infection (SWI) ,8. PostoIn patients with hyperglycaemia requiring urgent surgery, intravenous perioperative insulin infusion is the most effective method of rapidly achieving glycaemic control. The Society of Thoracic Surgeons (STS) currently recommends maintaining perioperative glucose levels < 180 mg/dL in patients undergoing cardiac surgery .Patients should be encouraged to stop smoking at least 30 days before cardiac surgery.Evidence level 2+. Strong recommendation, moderate quality of evidence.Smoking cessation has consistently been shown to provide important benefits in reducing complications in patients undergoing surgery . Resultsp = 0.01), readmission into the intensive care unit (ICU)  and infection , in non-smokers [In a large prospective study, Nagachinta et al. found that smoking was an independent risk factor for mediastinal infection after cardiac surgery . In a si-smokers .Quitting smoking for at least 30 days before surgery reduces the risk of PSM.We recommend that obese or overweight patients should be encouraged to lose weight before surgery; we also recommend adjusting prophylactic antimicrobials doses, reinforcing the preparation of the surgical field and ensuring a very stable wound closure to avoid dehiscence, besides systematic closure with a NPWT device.Evidence level 2++. Strong recommendation, moderate quality of evidence.Obesity, defined as a body mass index (BMI) > 30, is a well-recognised independent risk factor for PSM, as has been demonstrated in at least 20 clinical studies ,43,44,45Existing evidence does not support the benefit of preoperative chlorhexidine showers over other products.Evidence level 1+. Strong recommendation, high quality of evidence.When hair removal is considered necessary, we recommend the use of a depilatory cream or an electric razor, never a blade.Evidence level 1+. Strong recommendation, high quality of evidence.In patients who will undergo cardiac surgery, a wide range of prophylactic regimens based on non-antibiotic measures are currently used. Among the most frequent ones are those aimed at preparing the surgical area either using disinfectant solutions and/or depilation. In one series, preoperative chlorhexidine showers or baths reduced bacterial colonisation of the skin, but were not associated with a clear reduction in SWI . A systeShaving with cutting materials causes mild erosions to the patient that result in the accumulation of blood, facilitating bacterial overgrowth at human body temperature ,57. WhenS. aureus nasal carriage and proceed with its eradication if possible or time allowable in positive patients before cardiac surgery.We recommend knowing the state of Evidence level 1−. Strong recommendation, moderate quality of evidence.S. aureus is a major nosocomial pathogen worldwide [S. aureus infections may have serious consequences—including SWIs—which consequently delay healing, extend hospital stay, increase antibiotic use, cause unnecessary pain, increase hospital costs, and may lead to the need for further intervention or even cause death.orldwide . S. aureS. aureus infections are caused by the patients’ own colonising bacteria [S. aureus colonises the skin and mucous membranes of humans, the nose being the most common site [S. aureus in the nose is considered a well-defined risk factor for subsequent infection. Thus, it is recommended to know the nasal carrier status in all patients who will undergo MHS. The most common risk factor for increased likelihood of post-surgical staphylococcal infections, including mediastinitis, is sensitive or/and methicillin-resistant S. aureus nasal carriage [p = 0.002). In particular, lower respiratory tract infections and deep surgical site infections were less common in the chlorhexidine gluconate group than in the placebo group .Since the consequences of these infections may be extremely serious, effective prevention strategies are necessary. More than 80% of bacteria ,61. S. amon site . Currentcarriage ,64,65,66carriage . A prospAlthough some mupirocin and chlorhexidine resistance has been reported, results in a large sample of MRSA isolates collected during the REDUCE-MRSA trial reported that decreased susceptibility to Chlorhexidine (CHG), as measured by CHG MICs and carriage of qacA or qacB, was rare and was similar in frequency among MRSA isolates identified in decolonisation arms and in the screening and isolation arm. On the other hand, the prevalence of mupirocin resistance at baseline was moderate (7.1% LLMR and 7.5% HLMR), and the odds of mupirocin resistance during the intervention versus the baseline period did not differ between the targeted or universal decolonisation arms. To date, mupirocin and chlorhexidine resistance should not be of concern, but periodic surveillance studies are recommended.S. aureus nasal carriage within 15 days prior to cardiac surgery.We recommend the evaluation of Evidence level 1++. Strong recommendation, moderate quality of evidence.PCR-based techniques are recommended when a rapid screening method is required due to its high negative predictive value.Evidence level 1++. Strong recommendation, moderate quality of evidence.S. aureus carriage should ideally be performed within two weeks prior to surgery, since recolonisation is common in patients who had previously been treated for the same diagnosis [S. aureus after leaving the operating room. Moreover, 37% of cardiac surgeries are urgent [Assessing iagnosis . Howeveriagnosis  of the pe urgent  with no S. aureus (MRSA) and are considered negative after an incubation time of 72 h [S. aureus, a definitive identification/antimicrobial susceptibility test must be carried out. This process may last between 3 and 6 days.The most common technique to determine carriage in nose cultures is by swabbing both nostrils and placing the samples in transport media. Cultures from other sites  are not recommended . Followi of 72 h . In caseMolecular polymerase chain reaction (PCR) techniques allow much faster detection (1.5 h) and provide information on whether the microorganism is MSSA or MRSA. Simple techniques are commercially available, although the cost is much higher than that of a regular culture . The maiTo date, there is no evidence that supports the usefulness of post-decolonisation verification sampling.We recommend topical mupirocin for nasal decontamination in combination with chlorhexidine for skin decontamination.Evidence level 1+. Strong recommendation, high quality of evidence.We suggest systematic decontamination in patients in whom nasal carrier status cannot be assessed in a timely manner.Evidence level 3. Strong recommendation, low quality of evidence S. aureus decolonisation. Mupirocin ointment is one of the most popular antibiotics in clinical practice. It is often used to eradicate S. aureus because of its microbiological efficacy, safety and low cost [Antibiotics or topical antiseptics are recognised methods for low cost . Other pCompared to antibiotics, antiseptics often target a wide range of microorganisms and may reduce the presence of other co-pathogens . AntisepS. aureus from the nose, although early nasal recolonisation is common [S. aureus decolonisation is beneficial in patients undergoing major surgery or prolonged stays in ICUs [Doebbeling et al. found that mupirocin is effective in rapidly removing s common . A few ws common ,78,79. O in ICUs ,80.S. aureus before cardiac surgery, decolonisation is recommended until the result is known.In patients from whom it is not possible to have information on the nasal carrier status of We recommend chlorhexidine over povidone-based preparations for skin preparation in cardiac surgery.Evidence level 2+. Strong recommendation, moderate quality of evidence.The action of chlorhexidine (CH) or povidone iodine (PI) is slower and more superficial than that of alcohol. Moreover, CH persists in the skin for a significantly longer period. Hence, the use of alcoholic chlorhexidine (at CH concentrations greater than 0.5%) has been invoked because it combines the fast microbicide action of alcohol and the residual activity (persistence) of CH in the skin. The different formulations and application strategies of both compounds make it difficult to draw conclusions from studies addressing this question. A Cochrane Systematic Review carried out in 2015  comparedResults from randomised trials favour chlorhexidine. However, these trials did not focus on MHS ,83,84,85In two of the trials, one of the above-mentioned antiseptics was included and compared against another compound. In a German record of nearly 3000 patients, a comparison between CH combined with isopropyl alcohol (IPA) against IPA alone was carried out and, although the combination resulted in a lower number of mediastinitis cases than with IPA alone, non-randomisation and different alcohol concentrations between the two preparations do not provide much strength to the study .A randomised three-arm study in an American centre  comparedIn a randomised study, Stevens et al. assessed the possible benefit of adding a plastic adhesive to the skin after the application of the alcoholic chlorhexidine paint, but the authors concluded that the plastic did not provide an extra benefit regarding bacterial growth or time to wound recolonisation .We recommend the control of blood glucose level during surgery (preferably with continuous insulin infusion), keeping it within 110 and 180 mg/dL.Evidence level 2+. Strong recommendation, moderate quality of evidence.Hyperglycaemia and diabetes are known risk factors for the development of surgical site infections in patients who undergo MHS. Several studies suggest that perioperative hyperglycaemia poses an additional risk for infection among diabetics. Intra- and postoperative insulin administration protocols have been implemented.A meta-analysis of 29 randomised trials  . The first included more than 4600 coronary patients but it was not oriented to wound infection . The secWe do not recommend the systematic collection of surveillance cultures at the time of closure of the mediastinal.Evidence level 2+. Strong recommendation, moderate quality of evidenceAs with other surgical wound infections (SWIs), one of the accepted theories regarding the pathogenesis of postoperative mediastinitis is that most causative microorganisms are acquired in the operating room, while wounds and tissues are exposed to the surrounding environment, and less frequently by haematogenous spreading . Thus, cIn a prospective study, Bouza et al.  obtainedWe recommend CT-guided puncture in patients whom retrosternal sample collection is performed and when there are no other means to confirm the aetiological diagnosis.Evidence level 3. Strong recommendation, low quality of evidence.Staphylococcus (CNS) and Propionibacterium spp. isolates may indicate skin contamination. Computed tomography (CT)-guided puncture is useful in patients to whom mediastinal collection of samples is carried out when there is suspicion of infection. Being an invasive procedure, it is not free of adverse effects and, therefore, should ideally be performed by an expert.Retrosternal aspiration may be useful in patients with suspected mediastinitis and with postoperative sepsis, particularly in the absence of local signs of sternotomy infection . In 1984, Sarr et al. performed blind subxiphoid mediastinal aspiration in patients with fever and leucocytosis after MHS in cases without drainage or sternal instability. Early diagnosis was possible in 9 out of 24 punctured patients . BenloloWe recommend that cultures from sites that do not represent normally sterile tissues or fluids should be interpreted with caution, since they do not always allow determination of the causative agent of mediastinitis. The identification of the microorganism and its repeated isolation along with the clinical findings might be useful for the interpretation of the results.Evidence level 3. Strong recommendation, low quality of evidence.The list of criteria for surgical site infections used by the National Nosocomial Infection Surveillance System (Centres for Disease Control (CDC)) includes signs and symptoms that can be directly observed by the surgeon, such as wound dehiscence or fistulous tracts. The system also offers the possibility of using a microbiological criterion, e.g., presence of microorganisms isolated from fluids or tissue cultures aseptically obtained from the organ or space. However, there are no specific requirements for cultures, species identification, strain typing and interpretation of the bacteriological findings.In many PSM studies, a positive culture is required in addition to observable signs and symptoms. This requirement may serve to limit the accuracy of the diagnosis, since even in cases with undoubted and visible signs of infection, cultures may result negative due to the antibiotics administered to the patient before or after the surgery.Most post-sternotomy mediastinitis series present grouped microbiological isolates of blood cultures, wound, drainage and surgical samples, and few series provide a correlation between the various types of samples ,97,98. IWe do not recommend the systematic epicardial pacing wire cultures for early diagnosis of mediastinitis in the absence of clinical signs of infection.Evidence level 2+. Strong recommendation, moderate quality of evidence.S. aureus was the most common pathogen (81.25%). The authors identified 458 true-negative, 12 true-positive, 91 false-positive and 4 false-negative results. Therefore, cultures of epicardial pacing wires for the diagnosis of mediastinitis have a sensitivity of 75%, specificity of 83.4%, positive predictive value of 11.6% and negative predictive value of 99.1%.A few procedures to obtain samples of the anterior mediastinum have been described in the literature. These include retrosternal aspiration through sternotomy and subxiphoid retrosternal aspiration. However, the main risks of these two methods are lesions of the epicardial vessels, vascular grafts or the heart wall. Due to their location, epicardial pacemaker wires can be considered a good sample of the anterior mediastinum. In a study by Maroto et al. , epicardEven though the literature is scarce, some authors state that cultures of pacemaker electrodes removed between the seventh and ninth postoperative day may be useful for diagnosis, although a high percentage of false-positive results have been reported ,102,103.We recommend that the interpretation of bacterial culture results other than those from the original samples, surfaces or non-sterile tissue monitoring samples must be carried out individually. Their potential significance will depend on the type of microorganism, the collection site and the clinical picture.Evidence level 3. Strong recommendation, low quality of evidence.Candida spp. In addition, the authors identified several risk factors for secondary infection, such as the need of more than one revision surgery and closure of the sternum by muscle flap. It is worth mentioning the findings of Rodriguez Cetina et al. [In a work by Chan et al. , the auta et al. , who shoS. aureus, Gram-negative bacilli, Enterococcus and Candida spp., resembling tertiary peritonitis and thus requiring more complex therapeutic strategies. On the other hand, in patients who undergo treatment with NPWT or other delayed closure modalities, it is not essential for wound cultures to be negative prior to sternotomy closure.Identification of new microbial isolates throughout the progression of patients who underwent sternotomy cleaning and debridement surgery must be interpreted individually. The microbiology of infected sternotomies that failed the first medical-surgical approach is frequently associated with polymicrobial infections : methiciS. aureus.We recommend considering the presence of significant bacteraemia with no other clear origin in the 90 days after surgery as potentially indicative of mediastinitis, particularly when the isolate is Evidence level 2+. Strong recommendation, low quality of evidence.S. aureus was significantly higher in patients with sternal wound infection than in patients without infection, although this difference was not observed for other microorganisms. Interestingly, there were significantly more patients with continuous bacteraemia (positive blood cultures for at least two days) in the sternal wound infection group than in the group without sternal infection. Although the data from the study by Nakamura et al. are similar to those of other authors, it should be considered that it was a retrospective study, limited to a single centre, the sample size was small, and the authors did not include afebrile patients. Even though data in the literature are limited, it seems evident that in patients with febrile processes throughout the 90 days post-MHS, positive blood cultures have a high positive predictive value, particularly in cases of infection by S. aureus, but not by other microorganisms. The result is particularly significant for blood cultures grown in the second or third postoperative week.Although the diagnosis is difficult to predict clinically, some researchers have suggested that the presence of bacteraemia is highly suggestive of mediastinitis . Fowler We do not recommend the routine use of non-culture-based methods for the aetiological diagnosis of mediastinitis.Evidence level 3. Strong recommendation, low quality of evidence.Molecular methods may be considered in patients with mediastinitis and previous negative cultures or those receiving antimicrobials at the time of the intervention and deep sampling.Evidence level 3. Strong recommendation, low quality of evidence.There are currently two types of molecular techniques. The first are those that focus on positive cultures generally requiring days or a growth phase of 4 to 8 h followed by DNA extraction, purification and PCR-based amplification. A second group of techniques consists of those directly applied to the samples obtained from the patient, allowing faster results.Both types of techniques shorten the time of pathogen identification. In addition, they are attractive alternatives when conventional microbiological techniques fail to establish the microorganisms, particularly those that are slow growing, demanding, non-culturable, or when antimicrobial therapy may produce false-negative culture results. Rampini et al. highlighted the importance of 16S RNA PCR, which allows a pathogen to be identified in 42.9% of culture-negative samples in patients with evidence of infection . HoweverBrucella, Coxiella and Bartonella), deep mediastinal samples for 16S and 18S  PCRs and cultures in special media for Mycoplasma spp., Ureaplasma spp., Legionella spp., Nocardia spp., Fungi and Mycobacteria.We recommend that for the diagnostic approach in negative culture cases, determinations should include: specific serological tests  PCRs and cultures in special media for M. chimaera, despite being a very uncommon pathology, the European Centre for Disease Prevention [M. chimaera infections associated with open heart surgery based on three criteria: (i) any of the clinical criteria, including prosthetic valve or vascular infection, localised infection, and disseminated infection; (ii) exposure criteria, e.g., having undergone surgery requiring cardiopulmonary bypass in the 5 years prior to the onset of symptoms of infection; (iii) microbiological criteria, e.g., M. chimaera detected by culture or identified by DNA sequencing in an invasive sample.With regard to evention  and the evention  have forM. chimaera from peripheral blood is the most common method of microbiological diagnosis [Culture of iagnosis . Its senPlain X-rays are of limited use for the diagnosis of mediastinitis. We do not recommend their use as the first-choice diagnostic imaging test.Evidence level 2+. Strong recommendation, moderate quality of evidence.A plain radiograph has very limited use for the diagnosis of PSM. Mediastinal widening, usually due to postoperative haemorrhage and oedema, is often difficult to distinguish from the mediastinal widening in mediastinitis ,115,116.The presence of a displacement, rotation or rupture of suture wires or a widening of the sternal midline greater than 3 mm in a chest X-ray are very frequent findings in patients with dehiscence and their observation should make it suspect ,118,119.-As a first-choice diagnostic imaging technique in post-surgical mediastinitis preferably at week 2 after the surgery, when gas or normal collections of the immediate post-surgery period are potentially not present.-In patients with fever and leucocytosis without signs of infection or sternal wound drainage.-In patients with wound infection, to establish the extent of the infection. For sternal wound assessment in patients with suspected dehiscence (multiplanar reconstructions).-As a guide for sampling.We recommend performing a CT scan in the following cases:Evidence level 2+. Strong recommendation, moderate evidence quality.To date, CT scans are the most widely used imaging technique for assessing patients with suspected mediastinitis. It has a sensitivity of 25 to 100% (in most series above 67%) and a specificity of 33 to 100% ,124,125.CT scans are also useful for determining the extent of the infection  ,128,129,A separation of the sternal fragments > 4 mm or a separation in successive studies on a CT scan suggests dehiscence. Multiplane reconstructions and volume rendering may also provide information on the location of the sternotomy line (median or paramedian) and the wires. A paramedian incision, and the displacement, rotation, or rupture of wires, are frequent findings in patients with sternal dehiscence ,117,126.The presence of osteomyelitis may go unnoticed in initial periods in a CT scan; although, in advanced phases, it is possible to detect it ,117.In patients with fever and leucocytosis without signs of infection or sternal wound drainage. In these patients, a CT scan may allow a diagnosis of mediastinitis or an alternative diagnosis to be established . As repoPatients with wound infection, in order to establish the extent of the infection. In these cases, it is possible to differentiate between skin wound, pre-sternal or deep infection. The precise location of the lesions and their extent are of great help when planning surgical treatment ,128,129.Evaluation of sternal suture in patients with suspected dehiscence. The axial image and the reconstructions in multiple planes/3D allow the precise assessment of the degree of separation of the sternal fragments, existence or not of finishing, location of the incision (median or paramedian), condition of the wires, presence or absence of transverse fractures, etc. This information is of great interest when considering the treatment ,117,126.In specific cases, as a guide for sampling. Several works  address the usefulness of CT scans as guides for sampling ,126. AccOverall, we recommend the use of CT scans in the following cases:We do not recommend the routine use of MRI, as there are few available data and wires can cause artefacts.Evidence level 3. Strong recommendation, low quality of evidence.Nuclear medicine techniques may be useful in the evaluation of sternal osteomyelitis.Evidence level 2+. Strong recommendation, moderate quality of evidence.There is not enough evidence to recommend the routine use of PET-CT in patients with suspected mediastinitis. However, it may be useful in cases with suspected chronic infection, as well as for monitoring response to treatment.Evidence level 3. Strong recommendation, low quality of evidence.Magnetic resonance imaging (MRI) is a diagnostic test rarely used in patients with suspected mediastinitis. Wires used in sternal suture may cause artefacts, hindering the assessment of the mediastinum ,127,131.Nuclear medicine studies with Tc-99 m HMPAO-labelled leukocytes ,139,140,Recently published evidence supports the use of positron emission tomography-computed tomography (PET-CT) as a useful tool for the diagnosis and follow-up of infections associated with cardiovascular infection, particularly those related to cardiac devices. Its use in the field of mediastinitis is limited. Read et al.  showed tWe recommend performing a CT scan whenever there are signs of infection, despite the scarce information in the literature on this topic.Evidence level 3. Strong recommendation, low quality of evidence.Imaging tests in patients with clear mediastinitis may be of help in surgical planning. Furthermore, it will allow evaluation of the extent of sternal infection and the degree of involvement of adjacent structures . To dateSurgical management is an essential element for mediastinitis; however, there is no literature that specifies the exact best time for the surgical treatment of mediastinitis nor are there any comparative and prospective studies that would allow a clear choice of the most effective surgical technique. We understand that the general recommendations to treat deep skin and soft tissue infection are followed and, therefore, it should be performed as soon as possible, once the patient’s hemodynamic and clinical stability is achieved.We do not recommend the use of topical antibiotics on the surgical site prior to closure.Evidence level 2+. Strong recommendation, with moderate quality of evidence.Several studies show that topical antibiotics, applied directly or sprayed, ensure much higher local concentrations in the wound than systemic antibiotics, and that this high concentration persists for several hours after wound closure . TopicalThe cost-effectiveness of the results, the possible toxicity of some drugs  and the classic presence of resistance selection mean that prophylactic antimicrobial use with topical antibiotics is no longer a reality for most surgical services.We recommend the use of surgical steel wires to close the sternum. Superiority in reducing the incidence of mediastinitis has not been shown for other evaluated alternatives.Evidence level 1+. Strong recommendation, high quality of evidence.There are several surgical procedures and tools  for closure, but none have been widely adopted.Sternum wires. They are the most commonly used material and the majority of studies compare them with other closure systems or techniques. In a multicentre randomised study with high-risk patients , convent®, Praesidia SRL, Bologna, Italy) [®) [® tape  (braided Dacron) [Nevertheless, a randomised study showed that conventional closure with surgical steel wires is superior to polyester suture  . In addi, Italy) , there waly) [®)  and clos Dacron) ; and in  Dacron) .Other prevention systems. A randomised trial  on coronIn high-risk patients, we recommend the use of prophylactic negative pressure wound therapy to reduce the incidence of infection.Evidence level 2+. Strong recommendation, moderate quality of evidence.Good correlation has been reported between universal surgical risk estimation systems and the incidence of surgical wound infection . A studyProphylactic closed NPWT, e.g., Prevena (KCI) or PICO (Smith and Nephew), help keep wound edges together to avoid dehiscence, reduce lateral tension and oedema, increase tissue perfusion, stimulate granulation tissue formation, reduce bacterial colonisation and isolate the wound from potential contaminating sources. In one prospective study ,171 withBesides the two consensus conferences in which the use of NPWT was strongly advised, there is a volume of evidence for cases presenting one or more high risk factors or in subjects undergoing cardiac or pulmonary transplantation ,173. ThiComplications related to the surgical treatment of DSWI are usually minor; however, life-threatening bleeding can occur. These are usually due to the rupture of the right ventricle (RV) that has been reported both following conventional treatment and negative pressure wound therapy. However, this risk can be decreased by ensuring sternal stability and possibly by releasing retrosternal adhesions after wire removal; it is also advisable that an experienced surgeon should perform NPWT revisions in an operating room.We recommend the use of postoperative sternal immobilisation systems in all patients who undergo major cardiac surgery.Evidence level 2+. Strong recommendation, moderate quality of evidence.Postoperative sternal instability due to dehiscence or infection is a serious complication that may result in increased morbidity or hospital stay, the need for reintervention and greater cost. It may also increase mortality to as much as 25%. In this scenario, it is important to establish preventive strategies and additional postoperative measures, including the use of thoracic immobilisation systems.Prospective randomised studies have been conducted to assess the effectiveness of these immobilisation systems, as well as their ability to prevent sternal complications during the postoperative period after cardiac surgery.p = 0.047), such as dehiscence , deep infection (0% vs. 1.99%) and superficial infection (0.6% vs. 1.1% p = 0.417). In addition, hospitalisation time for complications was significantly shorter in the vest group (14.7 ± 707) compared to the control group . These findings have been validated in two randomised prospective multicentre studies, in which routine use of the vest implied significant prevention of sternal dehiscence and decreased the relative risk of complications from deep infection [The vest  consistsnfection ,178.We do not recommend mediastinal lavage on a routine basis, except in patients in whom NPWT cannot be performed or who require immediate closure. Povidone iodine should not be used in any case.Evidence level 2+. Strong recommendation, low quality of evidence.Conventional treatment of patients with mediastinitis after median sternotomy usually includes surgical revision, closure with mediastinal lavage, or reconstruction with omentoplasty or pectoralis plasty, and more recently, treatment with NPWT ,181,182.However, NPWT provides new possibilities. Several articles ,182,186 In patients who have no other choice but to undergo a mediastinal lavage, it should not be maintained beyond one week. Moreover, negative drainage cultures should not be used as criteria for withdrawing or maintaining the tubes ,187. In We recommend choosing the surgical reconstruction technique according to the stage, sternal stability and bone viability.Evidence level 2+. Strong recommendation, low quality of evidence.We did not find any randomised studies comparing surgical sternal reconstruction techniques. Most of the works are observational, cohort, case series and isolated case reports. Two meta-analyses support the use of NPWT during the initial management of sternal wound infections ,190. In There are numerous classifications of mediastinitis: Pairolero and Arnold , Oakley Current evidence supports the use of NPWT as a first-line treatment or bridge for surgical closure (IB) ,208,209.Recent studies suggest that the initial application of NPWT followed by sternal rewiring or plates and coverage by muscle flaps improves the results of sternal reconstruction; the use of NPWT is recommended over continuous irrigation systems .After sternal stabilisation, coverage with bilateral pectoral muscle advancement flaps ,221,222 In cases of significant sternal destruction, muscle flap coverage is necessary to provide stability to the chest and improve wound vascularisation ,226. DifCandida), in diabetic patients or the visualisation of prosthetic material [Omental flaps have angiogenic properties, are a source of granulation tissue and are more effective against infection ,230,231.material ,238,239.We recommend using BITA grafts in low-risk patients.We recommend skeletonised BITA grafting in diabetic patients with multivessel CAD.If there are any other related risk factors, the use of BITA must be individualised, taking into account the risk vs. benefit of the procedure. When its benefit is not clear, the use of BITA should be avoided.Evidence level 3. Strong recommendation, low quality of evidence.The use of bilateral internal thoracic arteries (BITA) grafting during myocardial revascularisation reportedly provides a survival benefit over single internal thoracic artery (SITA) grafting .However, the use of BITA may play a role in the development of DSWI because the vascularisation of both sides of the sternal wound is compromised. Techniques aiming to preserve a better sternal vascularisation such as skeletonisation or the use of harmonic scalpel have developed over the years .Factors such as obesity, COPD, female gender, old age, diabetes mellitus, renal failure and peripheral vascular disease may play a role in the development of DSWI  when BITA review of the literature on this topic shows that BITA grafts do not seem to increase the rate of DSWI in patients at low risk for mediastinitis.As reported by De Paulis (2005), in diabetic patients, as a single risk factor, BITA grafts do not seem to increase the rate of DSWI if both mammary arteries are used skeletonised rather than pediculated . When otWe do not recommend delaying surgical closure based on the persistence of positive cultures.Evidence level 3. Strong recommendation, low quality of evidence.The incidence of recurrence of sternal infection after initial reconstruction has been estimated to be between 5 and 10% ,222. AltBacteraemia, wound depth > 4 cm, degree of exposure and sternal instability have also been associated with the risk of recurrence of infection after closure . Plasma Although recent articles ,232 suggWe recommend applying NPWT considering the following: the stability of the sternum, as a curative method (with or without surgery) in patients with stable sternum, or as a bridge technique in preparation for surgery in subjects with an unstable sternum. NPWT should be checked every two to three days and last no longer than three weeks.Evidence level 2+. Strong recommendation, moderate quality of evidence.Argenta and Morykwas introduced this therapy in the 1990s  and it bThe knowledge and experience of NPWT is established and accepted. It is thought to stimulate the growth of granulation tissue , extractWe recommend changing the system and carrying out visual inspection every 48 to 72 h, which can be used to obtain culture samples.In adults with signs and symptoms of severe acute infection, we recommend initiating empirical antibiotic treatment as soon as there is clinical suspicion of mediastinitis.In non-critical adults, empirical treatment can wait for targeted treatment, based on laboratory findings.Evidence level 3. Strong recommendation, low quality of evidence.We did not find a high level of evidence nor high-quality studies, i.e., clinical trials, cohort or case–control studies, on when is the best time to start empirical antimicrobial treatment. Most of the literature refers to case presentations or reviews of the topic. Two articles assess mortality in patients with mediastinitis. The recommendation in these works for acute mediastinitis is to initiate early antibiotic treatment  ,262. In Staphylococcus coverage for the empirical treatment depending on local susceptibility pattern.In critically ill adult patients for whom aetiological confirmation is a threat, we recommend including methicillin-resistant Evidence level 4. Conditioned recommendation based on expert opinion. Very low level of evidence.Evidence on treatments targeted to specific microorganisms in patients who develop mediastinitis is scarce and of poor quality. It is limited to retrospective studies or case series with a small number of patients ,265,266.staphylococci causing the infections in more than 60% of the cases [Mediastinitis secondary to cardiothoracic surgery is mainly caused by Gram-positive cocci, with he cases ,268. Morhe cases  and Karrhe cases  showed tS. aureus, coagulase-negative staphylococci (CNS) are a very frequent cause of mediastinitis and that these microorganisms are usually resistant to methicillin everywhere. Therefore, it seems reasonable that empirical treatment should offer coverage against methicillin-resistant staphylococci, not only to cover S. aureus but also coagulase-negative staphylococci  [Several series show that the proportion of cases of mediastinitis caused by GNB ranges between 15 and 25% ,270. In = 0.004) ,271.P. aeruginosa , followed by A. baumannii , Enterobacter cloacae , and other Gram-negative pathogens .In a recent study published by Ma et al. in 170 patients , 87 GNB In addition to the above indicated figures, in recent years, there has been a high proliferation of GNBs that deserve to be described as multidrug resistant (MDR) and which lead to a worse prognosis.Overall, antifungal treatment should not be systematically included as part of the empirical treatment of PSM. It should only be administered in critical situations where there are risk factors for invasive fungal infection.Evidence level 4. Conditioned recommendation based on expert opinion. Very low level of evidence.The proportion of patients with postoperative mediastinitis of fungal aetiology is below 5%. In addition, the isolation of yeasts or filamentous fungi in a torpid course surgical wound is very difficult to distinguish from colonisation .We recommend that indications for empirical antifungal treatment be reduced exclusively in critically ill patients who have predisposing factors of invasive fungal infection, irrespective of the fact of having mediastinitisWith the current available information, it is not possible to recommend mediastinal irrigation either with antibiotics or antiseptic substances.Evidence level 3. Strong recommendation, low quality of evidence.Although topical irrigation of antimicrobial agents is a widely used practice by surgeons of different specialties, their use is uncontrolled and there are no studies in the literature with sufficient evidence to support or contradict their use.The purpose of mediastinal antibiotic irrigation is to achieve a very high local concentration  with low serum concentrations. However, there are no data on the effect that a continuous irrigation system has due to bathing the surgical site with high doses of antimicrobial solutions or the irrigation technique itself, which may have the advantage of washing out large amounts of fibrin, clots and detritus from the infected area. It is also unknown how much antimicrobial is absorbed through the mediastinum or pleural cavity, with the possibility of systemic side effects or resistance building.In 1963, Shumacker and Mandelbaum introduced for the first time a system of retrosternal lavage with antibiotics in patients with mediastinitis . NeomyciOther studies that use drugs to treat Gram-positive bacteria are usually retrospective, include a low number of cases and many factors that make interpretation difficult. Some only use animal models .The use of iodine povidone (IP) in irrigation was referred to as effective in the treatment of mediastinitis until the 1980s . SubsequIn a study by Truillet et al. of 19 cases, the authors describe the results of coverage of mediastinum with sugar, with rapid formation of granulation tissue and no evidence of side effects . SzerafiS. aureus) and against Gram-negative bacteria. The only published experiences on this are isolated case communications [Gentian violet seems to have replaced PI as an antiseptic in mediastinal irrigation due to its low toxicity and excellent anti-staphylococcal activity  in patients with methicillin-resistant staphylococcal infections.In enterococcal mediastinitis, particularly in bacteremic patients, it is recommended to follow the accepted scheme for endocarditis with double beta-lactam treatment (ampicillin + ceftriaxone) or the beta-lactam–aminoglycoside combination.These treatments always require expert consultation.Evidence level 3. Strong recommendation, low quality of evidence.Staphylococcus (CNS), MSSA, MRSA and Enterococcus spp. [Gram-positive bacteria are the most frequent cause of mediastinitis and, in decreasing order, the most frequent are: coagulase-negative cus spp. .We have not found any clinical trial with any drugs specifically performed in patients with mediastinitis. Therefore, recommendations regarding the indication of drugs and the duration of treatment should be interpreted with caution and derive from experience in other fields such as infectious endocarditis , infectiIn patients with MSSA, beta-lactams are the drugs of choice, particularly isoxazolyl penicillins (cloxacillin or oxacillin) or first-generation cephalosporins (cefazolin). According to recent studies, there is no evidence that either group of drugs is superior to the other in patients with bacteraemia and infective endocarditis . CefazolIf the causative agent is MRSA or CNS, where methicillin-resistance usually exceeds 50% of cases, the use of vancomycin or daptomycin is recommended as a first choice. At present, it seems sensible to use these first-choice drugs combining daptomycin with a second agent  for patients with MRSA isolates given the results in the field of bacteraemia. The most commonly recommended combinations are vancomycin/daptomycin-ceftaroline or daptomycin/vancomycin-fosfomycin see With regard to the association to rifampicin, it would be reserved for patients in which the prosthetic material could not be extracted and is supposedly infected .Alternatives to the first-line drugs mentioned above may be considered in different circumstances, but we insist that, to date, there are no clinical trials carried out in patients with mediastinitis. Ceftaroline may be a suitable agent as it is a beta-lactam with activity against MRSA. Oxazolidinones, such as linezolid and tedizolid, are an alternative but have not been evaluated in treatments of the duration required for mediastinitis. Its use is often performed sequentially and to complete an i.v. treatment with beta-lactams and/or glycopeptides, of which 15 or more days of treatment with good evolution have already been performed.The use of long half-life glycopeptides, such as dalbavancin or oritavancin, has been studied in skin and soft tissue infections but not in cases of mediastinitis. These drugs do not have an official indication for prolonged treatments as in the case of mediastinitis, although a single retrospective, observational, cohort study has shown optimistic results.It is difficult to give firm recommendations on the use of alternative agents such as cotrimoxazole, iclaprim, tigecycline, fosfomycin, etc., which should only be indicated under the indication and follow-up of an expert.Enterococcus is a less common cause of mediastinitis. In patients with beta-lactam-sensitive Enterococcus, as is generally the case with E. faecalis, we recommend the combination of ampicillin and ceftriaxone (using the accumulated data and experience in patients with endocarditis as criteria). Alternatively, the classic ampicillin and gentamicin regimen may be used, provided that resistance to gentamicin is of low profile and with an MIC < 500 ug/mL. This antibiotic combination is more nephrotoxic, and we consider it an alternative to the previous one and not as the primary recommendation. In patients with ampicillin- and vancomycin-resistant Enterococcus, treatment should be scheduled and followed by an expert. In some cases, the combination of daptomycin with a second drug  has been used successfully.Other Gram-positives are rarely causative agents of mediastinitis and their treatment should be agreed with by antibiotherapy experts.We recommend that the selection of antimicrobial treatment in patients with proven GNB mediastinitis must be adjusted in each circumstance and under expert supervision.Evidence level 3. Strong recommendation, low quality of evidence.K. pneumoniae 16.4%) [Although Gram-positive microorganisms are the cause of most cases of post-sternotomy mediastinitis, some authors have reported a prevalence of Gram-negative bacilli (GNB) infection of up to 56.7% (e 16.4%) .Targeted treatment of mediastinitis caused by GNB follows the same general criteria used for other types of infections. There are three possible situations: GNB with common sensitivity patterns, extended spectrum beta-lactamases (BLEE) GNB producers, and multidrug resistant GNB. We refer the reader to the more general references for these treatments ,300,301,We suggest using beta-lactams when possible.The duration of the treatment is always longer than in other soft tissue infections, usually varying between four and six weeks.In GNB mediastinitis also, it is acceptable to switch to oral treatment when drugs with adequate bioavailability and tolerance exist.In patients with MDR microorganisms, a drug association should normally be chosen, although the availability of new agents may make this recommendation obsolete.Given the prolonged treatment duration of these patients, it is particularly desirable to avoid the use of toxic agents such as colistin and aminoglycosides.Given the difficulties of therapeutic choice in these circumstances, they make the contribution of the infectious disease expert even more indispensable.We recommend confirming fungal mediastinitis before empirical treatment. The treatment described in Evidence level 3. Strong recommendation, low quality of evidence.Candida species are the most frequently reported microorganisms [Candida infection is limited to a few clinical cases [Although cases of fungal mediastinitis are anecdotal, they are associated with a high mortality rate. rganisms . Table 4rganisms ,304. Theal cases ,307,308.Malani et al.  suggest Aspergillus infections [Aspergillus infection in the sternum remains limited.Amphotericin B has historically been the primary drug of treatment for fections . Recent fections . HoweverWe recommend an average duration of four to six weeks in bacterial mediastinitis. When possible, we recommend switching to oral antimicrobials at week two to three.Evidence level 4. Conditioned recommendation based on expert opinion. Very low-grade quality of evidence.In case of sternal osteomyelitis and/or fungal mediastinitis, we recommend prolonged treatment.Evidence level 4. Conditioned recommendation based on expert opinion. Very low-grade quality of evidence.There are no comparative studies on the optimal duration of antibiotic treatment for patients with mediastinitis. Recommendations are based on clinical judgment, evolution of acute phase reactants, microbiological studies and imaging tests.The duration of treatment for bacterial mediastinitis is 4–6 weeks. Initial intravenous therapy is given for two weeks. After sternum closure, and if the results of antibiotic susceptibility tests allow it, it is recommended to switch to oral antibiotics, always considering the results of the antibiogram. If sternal osteomyelitis or foreign bodies (cerclages) are present, oral treatment may be prolonged.


CDC is the nation’s premier health promotion, prevention, and preparedness agency. As such, CDC is an important source of public health and clinical guidelines. If CDC guidelines are to be trusted by partners and the public, they must be clear, valid, and reliable. Methods and processes used in CDC guideline development should follow universally accepted standards. This report describes the standards required by CDC for the development of evidence-based guidelines. These standards cover topics such as guideline scoping, soliciting external input, summarizing evidence, and crafting recommendations. Following these standards can help minimize bias and enhance the quality and consistency of CDC guidelines. In its role as the nation’s premier health promotion, prevention, and preparedness agency, CDC is an important source of public health and clinical guidelines. In the late 1950s, data from the first-ever disease surveillance program created by Alexander Langmuir were used to issue the first national guidelines for influenza vaccine , and the Community Preventive Services Task Force (CPSTF)  assess the need for the proposed guideline; 2) determine guideline scope; 3) identify contributors, roles, and competing interests; 4) gather, summarize, and assess evidence; and 5) draft evidence-based recommendations. CDC’s Guideline Development and Reporting Checklist provides further details and examples of each standard  to lead development of these guidelines?If CDC is not responsible for leading the development effort, can a CDC partner develop the guidelines?Are adequate CDC resources available to develop the proposed guidelines?Is adequate time available to develop the guidelines?Is CDC able to publish, translate, distribute, and evaluate the guidelines?Affected Population: Developers might categorize affected populations by age , behavior , geography , occupation  or other criteria.Intended Audience: Public health guidelines often have diverse audiences ; therefore, they will need to balance the information according to multiple needs.Guideline Setting: Settings might include doctors or dental offices, hospitals, nursing homes, day care facilities, schools, colleges, workplaces, pharmacies, supermarkets, or the community at large. Settings might be narrowed by the populations they serve. For example, school-based guidelines might focus on schools in low-income areas, which could be determined by factors such as the proportion of children who are eligible for free school lunches.CDC guideline developers are encouraged to seek external input in the development of a guideline. The type and scope of a guideline affect the number of contributors and its complexity. Although interim guidelines might involve a relatively small group of internal agency experts, the development of standard guidelines might involve input from subject matter experts as well as individual and organizational stakeholders who might be affected by the implementation of the recommendations. Their inclusion in technical work groups and steering committees might help ensure the identification of potential issues that might affect guideline buy-in and adoption. Consultants and subject matter experts can contribute with input on selection of methods, interpretation of the evidence, and insight during the crafting of the recommendations. Other participants, such as official liaisons from stakeholder organizations, represent the views, concerns, and needs of their organizations and constituents.The Federal Advisory Committee Act (FACA) provides the framework for consulting with experts outside the federal government to provide advice on appropriate recommendations  formulate review questions, 2) develop the search protocol, 3) select relevant literature, 4) abstract and summarize the evidence, and 5) assess evidence quality.Guideline developers can use any appropriate framework for formulating the research questions for systematic reviews. The Population, Intervention, Comparison, Outcome (PICO) framework is one of the most frequently used  flow diagram  (Other guideline authorities, such as ACIP, USPSTF, and CPSTF, have adapted GRADE methods or developed alternative methods that are suitable for the type of evidence they deal with (The development of evidence-based recommendations involves using a body of evidence as the scientific backbone behind a recommendation. It should also consider well-established clinical or public health principles and anticipate adverse outcomes that most likely would happen if the recommendation is implemented (The standards described in this report are required for the development and reporting of CDC guidelines. Following these standards helps CDC guideline developers and their partners appropriately use evidence, minimize bias, and enhance quality and consistency. Observing these standards helps to make CDC guidelines worthy of the trust of the public and the health community. CDC standards and practices for developing guidelines will continue to evolve as advances in methods and technology offer the potential for more timely and useful guidelines. Machine learning has the potential to streamline time-consuming processes, such as searching for relevant evidence to inform guidelines (


Current first-line treatments for paediatric depression demonstrate mild-to-moderate effectiveness. This has spurred a growing body of literature on lifestyle recommendations pertaining to nutrition, sleep and exercise for treating paediatric depression.Paediatric depression clinical practice guidelines (CPGs) were reviewed for quality and to catalogue recommendations on nutrition, sleep and exercise made by higher-quality CPGs.Searches were conducted in Medline, EMBASE, PsycINFO, Web of Science and CINAHL, and grey literature CPGs databases for relevant CPGs. Eligible CPGs with a minimum or high-quality level, as determined by the Appraisal of Guidelines for Research and Evaluation, Second Edition instrument, were included if they were (a) paediatric; (b) CPGs, practice parameter or consensus or expert committee recommendations; (c) for depression; (d) the latest version and (e) lifestyle recommendations for nutrition, sleep or exercise. Key information extracted included author(s), language, year of publication, country, the institutional body issuing the CPG, target disorder, age group, lifestyle recommendation and the methods used to determine CPG lifestyle recommendations.Ten paediatric CPGs for depression with a minimum or high-quality level contained recommendations on nutrition, sleep or exercise. Lifestyle recommendations were predominately qualitative, with quantitative details only outlined in two CPGs for exercise. Most recommendations were brief general statements, with 50% lacking supporting evidence from the literature.Interest in lifestyle interventions for treatment in child and youth depression is growing. However, current CPG lifestyle recommendations for nutrition, sleep or exercise are based on expert opinion rather than clinical trials. These include cognitive–behavioural therapy (CBT), interpersonal psychotherapy and antidepressant medication.13 before considering the prescription of medication or referral into specialist mental healthcare. Specialist mental healthcare may also combine several treatment components. For example, CBT might be combined with psychoeducation and parental counselling. Lifestyle interventions for these and other lifestyle aspects not explicitly covered in this study (e.g. screen time) may be additional strategies used as part of such a sequence. Lifestyle interventions may also offer an approach to addressing depression in contexts where trained psychiatrists or clinical psychologists are not widely available, and where these interventions may provide low-stigma access to mental health treatment.During adolescence, life-shaping behaviours develop, including eating habits, sleep patterns and physical activity routines. These, in turn, can affect current and future health: emerging literature discussed in the following suggests some benefit to paediatric depression for lifestyle interventions such as improving nutrition, sleep and physical activity. Lifestyle interventions may be less resource-intensive compared with specialist psychotherapeutic interventions. For example, a relevant treatment plan might be prescribed and monitored by a primary care physician within a stepped-care model,14 Among cross-sectional studies, two recent systematic reviews without meta-analyses highlight an association between unhealthy diets and depressive symptoms among children and adolescents.16 Much needs to be gleaned about the physiological impact of suboptimal nutrition on brain function, but it is generally accepted that optimal brain function requires adequate levels of both macronutrients  and micronutrients .17 Ideal typical high-quality diets, such as the Mediterranean diet, are characterised by substantial intake of whole grains, fruits/vegetables and legumes; moderate amounts of fish, seafood, dairy, poultry and healthy fats; and low intake of red meat and sweets. They are thought to be beneficial because they are high in antioxidants, polyunsaturated fat, dietary fibre, vitamins and minerals; and low in saturated fat, simple sugar and processed food.18The field of nutritional psychiatry is in its infancy. A recent evidence gap map reveals a paucity of research, and especially randomised controlled trials, assessing micronutrients in the treatment of depression in children and adolescents.19 and is correlated with depression severity.20 To date, two meta-analyses have found an association between poor sleep quality and depression in adolescents.22 Clinical interventions to restore healthy sleep routines and good sleep quality have demonstrated improvements in depressive symptoms in youth. One small feasibility trial observed medium-sized effects of improved outcomes among youth diagnosed with both depression and insomnia, compared with a CBT and sleep hygiene control condition when CBT for depression was augmented with CBT for insomnia.23 A randomised controlled trial comparing a sleep extension intervention (involving bedtime scheduling and sleep hygiene advice) with an attention placebo in adolescents with chronic sleep reduction also found significant improvement in depressive symptoms in the intervention group, compared with the control group .24 Among this body of literature, such trials suggest that interventions are promising, although systematic reviews have not been conducted, as the evidence base for the effect of adjunctive or standalone sleep interventions remains scarce.23Sleep disturbance is one of the most common symptoms among adolescents with depression,25 Among children and adolescents with elevated or clinical levels of depressive symptoms, a moderate-to-large effect size for efficacy was reported in using physical activity interventions as treatment in two recent meta-analyses.27Low physical activity and high sedentary behaviour are emerging as risk factors for depression. The largest body of evidence for paediatric lifestyle interventions exists for exercise. A recent systematic review of reviews examining physical activity for the prevention of depression demonstrated a beneficial effect of exercise on depressive symptoms across all age groups, including children and adolescents.28 As adjunctive treatments, lifestyle interventions could possibly enhance the effectiveness of evidence-based psychotherapies or medication; in stepped-care13 models, clinicians may consider lifestyle interventions for the treatment of depressed youth, especially in primary care.Although the evidence base supporting lifestyle interventions for the treatment of youth depression is still comparatively scarce, there exists a growing interest in the active ingredients of treatment for depression.29 High-quality CPGs derived from the findings of rigorous systematic reviews and meta-analyses represent the highest level of evidence in evidence-based medicine. Their development involves systematic and methodologically rigorous procedures for reviewing and appraising the evidence, and deriving feasible, measurable and achievable recommendations.29 This umbrella review aims to investigate the extent to which nutrition, sleep and exercise interventions are part of current recommended practice for treating paediatric depression around the world; to critically examine the quality of the CPGs issuing relevant guidance; and finally, to catalogue recommendations made by high-quality CPGs.Clinical practice guidelines (CPGs) are defined as ‘systematically developed statements to assist practitioner and patient decisions about appropriate healthcare for specific clinical circumstances’.30 with considerations specific to CPGs.31An integral component of CPGs is a rigorous review of evidence-based methodology. To systematically review CPGs, we followed the Joanna Briggs Institute methodology for umbrella reviews,33 The database was updated and expanded to include CPGs published in English, French, German and Spanish (i.e. languages spoken within the study team), up until July 2020. There was no limit on geographical location.We drew on an existing database of CPGs for paediatric depression that was created as part of a previous systematic search, and included CPGs published in the English language between 2005 and July 2017.https://doi.org/10.1192/bjo.2021.1020) was developed by a research librarian. CPGs were retrieved from five bibliographic databases , and a thorough grey literature search in relevant CPGs databases ; websites of mental health-related organisations , governmental websites and a broad Google search.The search strategy  screened 10% of records in duplicate, yielding a high interrater agreement (κ = 0.86). All full texts in the database were screened for inclusion in this umbrella review in duplicate by two reviewers (K.R.K. and S.C.C.), with a high interrater agreement (κ = 0.90). Disagreements were resolved by discussion. Title and abstract screening were conducted with the web-based systematic review software EPPI-Reviewer version 4.0 .34 The full-text screening was conducted with Covidence web-based software .35For the creation of the initial CPGs database, titles and abstracts were screened by a methodologist and eligible full texts were then screened in duplicate for inclusion by two methodologists.Records were eligible if they were relevant to the paediatric population (<19 years of age); labelled as CPGs, practice parameter or consensus or expert committee recommendations; addressed psychosocial treatment for depressive disorder; were the latest version of the CPG; and contained any reference to lifestyle recommendations for nutrition, sleep or exercise. Lifestyle recommendations regarding nutrition, sleep or exercise could be brief standalone statements or detailed recommendations. CPGs were excluded if they contained only medication algorithms or were narrative or systematic literature reviews that contained no summary statements or algorithms regarding CPG recommendations.36 instrument, comprising 23 items with six domains. Two pairs of reviewers  appraised all English guidelines with the AGREE–II online software (https://www.agreetrust.org/agree-ii/). In cases when the overall scores differed by more than two points, all domains were reviewed, and final decisions were determined by consensus. German, French or Spanish CPGs were appraised by K.R.K. Three key domains of the AGREE-II were used to determine the quality of the CPGs: stakeholder involvement, the rigor of development and editorial independence. These three key domains have been used previously to assess the magnitude of the risk of bias in each CPG.32 AGREE-II scores of ≥70% indicated high quality, scores from 50 to <70% indicated minimum acceptable quality, and scores <50% indicated low quality. Only CPGs of minimum or high quality were included in this umbrella review.Eligible CPGs were assessed for quality with the Appraisal of Guidelines for Research and Evaluation, Second Edition (AGREE-II)31For systematic reviews of CPG recommendations, the Population, Intervention, Comparator, Outcome (PICO) statement is adapted into a PICAR statement, where P stands for the target population, clinical indication(s) and condition(s); I stands for target intervention(s); C stands for eligible comparators or comparisons, and key content; A stands for attributes of eligible CPGs and R stands for recommendation characteristics .31TableKey information was extracted from included CPGs as follows: author(s), language, year of publication, country (i.e. where the work was published or conducted), the institutional body issuing the CPG, target disorder, age group, lifestyle recommendation and methods used to determine CPG lifestyle recommendations. Extraction forms were pilot tested. Extraction was conducted in Microsoft Excel 2021 for Windowsby one reviewer (S.C.C. or K.R.K.), and verified by the second reviewer. Narrative passages extracted from foreign-language CPGs were translated for citation in this paper by K.R.K.n = 5) were specific to children and adolescents, three focused only on adolescents and two on adolescents and young adults. CPGs targeted treatment for general depression (n = 6), major depressive disorder/major depression (n = 2) and depressive disorders (n = 1). Based on quality ratings in the three key domains of the AGREE-II appraisal, five of the included CPGs were rated to be of high quality (AGREE-II score >70), and five CPG scored in the minimally acceptable range (AGREE-II score 50 to <70)  .Fig. 1SFour out of the five high-quality CPGs provided references to relevant primary evidence alongside the lifestyle recommendations, whereas four out of the five CPGs scoring in the minimally acceptable quality range did not reference evidence sources for their recommendations.37‘A child or young person with depression should be offered advice on the benefits of regular exercise and encouraged to consider following a structured and supervised exercise program of typically up to 3 sessions per week of moderate duration (45 min to 1 h) for between 10 and 12 weeks’.All eight recommendations related to nutrition were brief statements, suggesting ‘adequate/balanced nutrition’ or ‘healthy eating’, and were accompanied by sleep and/or exercise recommendations. Eight CPGs providing recommendations related to sleep made brief statements and supported general good sleep ‘habits’ or ‘patterns’ or ‘hygiene’. Sleep recommendations were accompanied by other lifestyle recommendations. Six of the eight CPGs providing exercise recommendations were general and included statements such as ‘benefits of regular exercise’ and ‘exercise routines’. Two CPGs provided more detailed recommendations concerning exercise and offered a quantitative component (see below) with citations from the literature. Both CPGs had a high-quality AGREE-II score in the three key domains. The first was the guideline issued by the National Institute for Health and Care Excellence (NICE) in the UK, which suggested that:38‘Studies suggest that group and supervised activities with an aerobic component and of moderate-low intensity (three times a week for at least seven weeks) may be the most appropriate option. However, the relatively small number of existing studies and their limitations should be taken into account. […] the preferences of the patients are essential when recommending physical exercise associated with the treatment plan, and both the possibility of its implementation and the clinical and psychosocial characteristics of the patient should be assessed. […] Therefore, since the evidence regarding the efficacy of physical exercise is limited, the advisability of its recommendation as part of the therapeutic strategy should be assessed individually, taking into account the patient's preferences, and provided that the severity of the picture does not hinder its realization.’The second CPG was issued by the Spanish government and recommended:Exercise recommendations were accompanied by sleep and/or nutrition in seven out of eight CPGs. Summary characteristics for included CPGs are outlined in This umbrella review is the first to summarise clinical practice recommendations for nutrition, sleep and exercise in the treatment of child and youth depression. We identified ten child and/or adolescent CPGs for depression that met the minimum AGREE-II quality criteria and contained recommendations on nutrition, sleep and/or exercise. Six CPGs included relevant recommendations, but did not meet quality criteria for inclusion in this umbrella review. Thirteen CPGs were disregarded because they did not make any mention of sleep, nutrition or exercise. Recommendations for nutrition, sleep and exercise provided by the included CPGs were predominately qualitative, stating the benefits of a balanced diet, healthy sleep and exercise. Quantitative details (e.g. exercise routine) were only outlined in two CPGs . Half ofVague recommendations place the onus of interpretation for individual treatment plans on clinicians, who may have limited training or expertise regarding the specific linkages between nutrition, sleep or exercise, and youth depression. Additional research and more specific recommendations are needed to help clinicians decide when, for whom and how lifestyle interventions are likely to be most effective, and whether they should be provided as adjunctive treatments alongside psychotherapy or medication, or as interventions in their own right.Although it might be argued that recommending a healthy lifestyle can do no harm, the possibility of harm arising from these interventions  was not explicitly appraised or discussed in the reviewed CPGs. When implementing stepped-care models, clinicians may decide to follow the broadly phrased lifestyle recommendations currently provided by CPGs, or prefer that youth try to increase exercise, modify their sleep routines or attempt to establish healthier eating patterns before prescribing higher-intensity treatments, such as supportive counselling, psychotherapy or medication. However, if lifestyle interventions were ineffective in alleviating depressive symptoms, prescribing them might cause unnecessary delays in providing proven evidence-based treatments.Adverse effects may also arise where youth perceive recommendations to make lifestyle changes as dismissive of the severity of their distress or impairment, or of a perceived need for more intensive support. It is also possible that prescribing a healthier lifestyle reinforces self-blame, where youth gain the impression that a personal failure to live a healthier lifestyle has caused their depression. Lifestyle prescriptions may also fuel arguments between parents and youth, where parents have already attempted to encourage more healthy eating, sleep and activity patterns. Similarly, severe depressive symptoms may interfere with a young person's ability to implement lifestyle advice, which may reinforce feelings of guilt and failure. Additionally, sedentary behaviour among parents may model sedentary lifestyle habits as normal, making such interventions more difficult to implement. For example, parents who are sedentary owing to health reasons, work or family commitments may not have time for exercise, and may inadvertently be modelling sedentary behaviour as normal.A lack of youth and/or family stakeholder involvement in the development of the CPGs (except for the NICE CPG) was one factor that contributed to the downgrading of AGREE-II scores. Future CPGs should seek to incorporate the perspective of youth, and appraise the cognitive and emotional effects that broadly phrased lifestyle recommendations might have when implemented in primary or routine specialist care.The strengths of this umbrella review relate to the systematic methodology applied herein, which included strict inclusion/exclusion criteria, duplicate screening, an AGREE-II quality assessment and the exclusion of CPGs that did not meet minimum quality cut-offs. Although not exhaustive, the inclusion of some non-English CPGs enabled the consideration of a more global sample of recommendations.17 sleep22 and exercise,39 on the development and maintenance of child and youth depression. However, there is limited evidence on the efficacy and effectiveness of these lifestyle factors as treatment ingredients, which is reflected by a lack of detail in the recommendations.Some limitations should be considered when interpreting the study findings. One is the limited capacity within the study for the duplicate quality assessment of French-, German- and Spanish-language CPGs, as well as the capacity to screen and include CPGs in other languages. Additionally, all the nutrition and sleep recommendations were brief statements and half of the included CPGs lacked citations to support the lifestyle recommendations made, making it impossible to review the quality of evidence underlying them. Of the 13 candidate paediatric depression CPGs  that were excluded because of a lack of recommendations regarding nutrition, sleep or exercise, it remains unclear whether they explicitly chose not to mention lifestyle recommendations because of the limited evidence base, or whether these lifestyle factors were not considered when reviewing the evidence for different treatment options. Other limitations relate to the body of primary evidence supporting lifestyle recommendations. There is a considerable epidemiological evidence base examining the impact of lifestyle factors, such as nutrition,40 Further research is needed to determine whether lifestyle interventions should precede more intensive interventions, whether they should be provided alongside other psychosocial interventions or medication, or whether they are most helpful when provided to youth who do not respond to evidence-based treatments. Multi-centre trials engaging youth across different treatment sites may be one avenue for increasing statistical power and, potentially, the representativeness of study samples to support robust conclusions for lifestyle interventions. Future research should also address the risks and benefits of each approach, including the use of lifestyle interventions in stepped-care models and primary care.As knowledge about the efficacy surrounding lifestyle interventions grows, the findings may support prescribing lifestyle changes to youth that are waitlisted to receive evidence-based treatments. As such, lifestyle interventions could be part of a wider catalogue of intervention strategies that youth can use without being directly accompanied by a health professional.In conclusion, there is some evidence that lifestyle interventions can have beneficial effects on depression, but research is still limited and there are very few well-designed, randomised controlled trials. Traditionally, interventions related to nutrition, sleep and exercise have not been included in the mental health toolbox. This umbrella review found that ten CPGs for paediatric depression with minimum or high quality contained mainly brief and non-specific statements concerning nutrition, sleep or exercise, that left room for multiple interpretations; for example, concrete treatment plans or dosage suggestions were rarely provided. Half of the included CPGs did not back their recommendations with references to the existing literature. Although the evidence base is growing, lifestyle recommendations are hampered by inadequate study designs and a field of study in the early stages.Future research should build on associations between nutrition, sleep or exercise and depressive symptoms. High-quality, multi-centred trials are needed that examine the effectiveness of lifestyle interventions as a precursor to higher-intensity treatments, as a concurrent treatment or as an option for treatment-resistant depression. Similarly, trials are needed that assess the benefits of using these interventions in different care settings , and across different socioeconomic and ethnic groups. Future studies should examine whether lifestyle interventions can have any adverse effects on young people's treatment motivation and well-being. It is important to include youth with lived experience of depression and their families in the design and interpretation of future studies, as well as in the formulation of future CPGs, to ensure relevant interventions are acceptable and meaningful to youth.This review suggests that lifestyle interventions as ingredients for treatment in child and youth depression hold promise and have been addressed in several high-quality CPGs. However, the current body of evidence needed to develop strong CPG recommendations is scant. Progress calls for further rigorous trials to fill key knowledge gaps regarding the role of these factors alone, and in combination with psychotherapy and medication.


Patients rightly expect us to provide them with the best possible medical treatment. Therefore, we have increasingly used and refined the principles of evidence-based medicine over the past two to three decades in our research. In the recent past, the evidence published in scientific journals and elsewhere has started to grow at an unprecedented pace, now nearly doubling every 4 years. On average, a new medical article is published every 15 s. To a growing extent, the evidence informing our clinical decision-making comes from our very own setting. However, there is not only a change in quantity: a growing number of today’s clinical trials also encompass patients’ preferences and include relevant details needed for implementation in clinical decision making.Increasing the quantity of evidence can in itself create a variety of new problems: health care professionals are challenged to remain up to date with new evidence like never before. Systematic reviews show that adherence to guideline recommendations in daily routine care varies from 20% to over 80%. Thus, despite rapidly growing knowledge, a varying share of patients are still likely to receive suboptimal treatments, inappropriate diagnostics, unsafe medications, and costly but ineffective care. Incorporating new evidence into daily practice already usually takes several years. This ‘evidence to practice gap’ might even get bigger the more evidence there is.At the same time, we still face an ongoing lack of evidence in other domains. This is partly due to the characteristics of research in primary care, for example, varying organisational structures, practice team compositions, or different contexts caused by the health care system and its legal boundaries. Besides these contextual factors, research in primary care frequently deals with complex interventions and patients with very heterogeneous characteristics, which leaves us with many potential sources of uncertainty when we try to put together guidelines based on evidence in our field of research.Fortunately, in the wake of digitisation, new and promising ways of combining and integrating evidence, for example, learning health care systems, big data analysis and machine learning, are at our disposal. Nonetheless, closing evidence gaps is an ongoing challenge that is only partially solved by creating new or more evidence or combining more and more information. In fact, we still have to perform constantly assess evidence gaps, both in generating evidence and in translating evidence into practice. Ideally, a prioritisation of research questions follows this assessment and, in addition, existing evidence gaps should be addressed in trials in real-world conditions.During the 92nd EGPRN meeting, a virtual conference on 30 April and 1 May 2021, gaps in evidence and ways to study evidence gaps in general practice and family medicine were discussed.


Pharmacists play a unique role in integrating genomic medicine and pharmacogenomics into the clinical practice and to translate pharmacogenomics from bench to bedside. However, the literature suggests that the knowledge gap in pharmacogenomics is a major challenge; therefore, developing pharmacists’ skills and literacy to achieve this anticipated role is highly important. We aim to conceptualize a personalized literacy framework for the adoption of genomic medicine and pharmacogenomics by pharmacists in the United Arab Emirates with possible regional and global relevance.A qualitative approach using focus groups was used to design and to guide the development of a pharmacogenomics literacy framework. The Health Literacy Skills framework was used as a guide to conceptualize the pharmacogenomics literacy for pharmacists. The framework included six major components with specific suggested factors to improve pharmacists’ pharmacogenomics literacy. Major components include individual inputs, demand, skills, knowledge, attitude and sociocultural factors.This framework confirms a holistic bottom-up approach toward the implementation of pharmacogenomics. Personalized medicine entails personalized efforts and frameworks. Similar framework can be created for other healthcare providers, patients and stakeholders. Pharmacogenomics (PGx) is a rapidly growing field of personalized medicine focusing on the effect of genetic variation in drug response , 2. It aPrescribing the right drug with the right dose to the patient from the first time is the anchor of PGx and personalized medicine . The AmeStudies show that pharmacists are faced with a plethora of needs, challenges and barriers that obstruct them from rising up to expectations. The literature emphasizes pharmacogenomic knowledge gap as a major challenge. In a study that interviewed pharmacists by Berenbrok et al. , particiNumerous studies have concluded that PGx literacy is the most cited barrier by pharmacists for the full implementation of PGx in the health setting; most of the pharmacists did not thoroughly study PGx during their coursework –25. A stPharmacists strive for the synthesis of a framework to tackle their PGx literacy to facilitate the full implementation of PGx. The literature supports this—an article by Wurcel et al.  called fThere is conflict among researchers about the definition of health literacy. For the PGx literacy, we define it based on Baker  as “the The Health Literacy Skills framework (HLS) of Squiers et al.  is a comHowever, limited studies propose a personalized framework for pharmacists and other healthcare providers addressing their PGx literacy. In this article, the pharmacogenomics/genomics literacy framework for pharmacists (PGLP) is introduced—a personalized literacy framework for the adoption of PGx by healthcare providers concerned with genomics in UAE with possible regional and global relevance. This framework will guide stakeholders in their mission of equipping pharmacists, genetic counselors, doctors and nurses with skills required for the adoption and implementation of PGx.The HLS framework captures a holistic approach toward literacy and takes into account individual and sociocultural influences; therefore, it was utilized to conceptualize the PGLP framework . MoreoveThe pharmacogenomics/genomics literacy framework for pharmacists (PGLP) were conceptualized based on the themes, codes and associations extracted and analyzed from the focus group discussions .The main themes and subthemes of pharmacists’ PGx knowledge and attitudes extracted from the focus group discussions are shown in Figs. Over a third of the participants perceived their current knowledge and understanding of PGx and genomics to be poor. They also reported having limited knowledge on where genetic testing is conducted in the UAE. When questioned on their higher education, both senior- and entry-level pharmacists stated they did not receive any formal education on PGx or genomics during their undergraduate pharmacy program. All clinical pharmacists noted a gap in the availability of resources by the UAE health authorities regarding information on genomics. Outpatient pharmacists were more familiar with the cost and accessibility of genetic testing.The majority of the pharmacists exhibited a positive attitude toward PGx despite their perceived lack of knowledge. However, there were some mixed responses on genetic testing. Some pharmacists were reluctant due to the possible discrimination and stigmatization associated with certain genetic diseases and the impact it could have on their social and family lives. Others viewed it as a protective measure allowing them to seek medical interventions and modify health behaviors in the case of a predisposition to a disease. Religious and cultural beliefs were noted as a potential barrier to the implementation of PGx in UAE.When inquired on their skill and ability in interpreting genetic test reports, all pharmacists agreed they were not completely inept.The main themes of knowledge and attitudes constitute the main pillars of the PGLP framework which are consistent with the components of the HLS framework including: (1) the individual input of pharmacists, (2) demand for genomics’ literacy, 3) skills needed to improve illiteracy, (4) knowledge of the pharmacists about genomics/PGx and its applications, (5) attitudes of pharmacists and (6) sociocultural influences  apprehended the same sociocultural factors that we appointed in our PGLP framework. Pang  named thPharmacists are not isolated from the community, health system or other healthcare providers. Consequently, pharmacists in our cohort advocate a multidisciplinary approach to implement PGx. Studies favored this methodology. Caraballo et al.  employedIn the literature, there is an aggregation of evidence of the PGx’s knowledge gap among healthcare providers in general –74 and pAssuring a competent healthcare workforce is one of the 10 Essential Public Health Services . It encoThis framework will guide stakeholders in their mission of equipping pharmacists, genetic counselors, doctors and nurses with skills required for the adoption and implementation of PGx. PGLP directs the attempts of stakeholders to educate pharmacists on PGx by taking into account their individual factors and tailoring modules to meet their roles, occupation and capabilities whether they are clinical, inpatient, outpatient or community pharmacists or pharmacists in a Pharmacy Therapeutic Committee (PTC) or Institutional Review Board (IRB).Stakeholders occupied by implementing PGx in their countries should not isolate their approach from the sociocultural factors incubating and nourishing their infrastructure and resources. They have to tailor their map to their current educational system, health system and culture. They have to utilize media and call for laws and policy. Moreover, they need to factor in religion and literacy of the community. The demand for PGx/genomics literacy will kick-start PGx implementation resulting in educational efforts and utilization of the PGLP framework.Catalyzing the three dynamic pillars of skills, knowledge and attitude of pharmacists or other healthcare providers will be a compelling formula for developing cost-effective personalized and profound modules and approaches. Knowing the pharmacists’ skills will guide the stakeholders in purchasing platforms, databases and other resources and will tailor orientation. Mapping the knowledge and attitude of the pharmacists will help shape the resources, workshops, seminars and competencies.This PGLP framework is comprehensive and we theorize that it will tailor the implementation strategies in a standardized and systematic manner.In conclusion, we believe that our framework can be a guide for the implementation of genomic medicine and PGx among pharmacists as it addresses a plethora of individual and sociocultural factors in addition to the skills, demands, knowledge and attitudes of pharmacists. This framework guarantees a holistic bottom-up approach toward PGx implementation. Personalized medicine entails personalized efforts and frameworks. Similar frameworks can be created for other healthcare providers, patients and stakeholders.The strength of our work is conceptualizing a novel, comprehensive and personalized PGx literacy theoretical framework tailored to pharmacists. Moreover, the PGLP framework is based on the validated theoretical HLS framework that was synthesized upon a number of literacy frameworks thus increasing the PGLP framework’s credibility . FurtherMoreover, this framework can be used to guide stakeholders in any country that are planning a strategy to implement PGx, as it is comprehensive and systematic. Additionally, this framework can be a platform to PGx literacy to other healthcare providers or even other health-related literacy. It is highly recommended to introduce new courses and training workshops for pharmacists to improve the chances of PGx application as knowledge is an essential and dynamic pillar for the implementation of genomic medicine and PGx. The glitch in navigations skills can be amended by the governing bodies by providing official clinical practice pathways and references for healthcare providers. The PGLP framework is a theoretical framework that needs to be validated. Future research on its implementation can validate this framework. We call researchers to test and validate this PGLP framework to pharmacists and extrapolate it to other healthcare providers.


Disaster science and scholarship are forever expanding and there are increasing calls to base disaster risk reduction policies on the evidence produced by such work. Using examples and argument, this opinion piece examines the nature of evidence. It defines evidence-based practice and considers how it has developed and become important to disaster risk reduction. A definition of what constitutes evidence is difficult to achieve but it must be made in relation to whether the data and information collected can usefully be interpreted and employed to change things for the better. Case histories from past and present centuries show that evidence can sometimes be argued over endlessly. In other cases it is roundly ignored. In yet other instances, false conclusions derived from evidence can become evidence in their own right. Nevertheless, there are situations in disaster risk reduction in which evidence is sorely needed but is clearly lacking. The effectiveness of counter-terrorism measures is one such area. In conclusion, evidence is valuable, above all if there is willingness to use it to support policy formulation, especially in a simple, transparent manner. Subjective interpretation can never be entirely removed from the use of evidence, and evidence alone will not stimulate the policy formulators to improve their decision making. Hard Times by Charles Dickens (1854)Now, what I want is, Facts. Teach these boys and girls nothing but Facts. Facts alone are wanted in life. Plant nothing else, and root out everything else. You can only form the minds of reasoning animals upon Facts: nothing else will ever be of any service to them. This is the principle on which I bring up my own children, and this is the principle on which I bring up these children. Stick to Facts, sir!—Thomas Gradgrind, in How much do governments, regulators, and risk managers want facts, and what do they consider to be evidence? At 0:54 a.m. on Wednesday, 14 June 2017, fire broke out in Grenfell Tower, a 24-story residential building in the Royal Borough of Kensington and Chelsea, London, England. The building burned for 24 hours, and at one point during the night a sheet of flame enveloped one entire side of the structure. Many people were trapped in their apartments. Seventy-two died, a similar number were injured and 400 people were left homeless . Data are a low-level form of evidence and may not be enough to form an adequate generalization about a phenomenon Rowley . DisasteThe Irish engineer Robert Mallet developed a strong interest in earthquakes. Indeed, he is to some extent the “Father of Observational Seismology.” One of his greatest achievements was to compile all the known evidence of earthquakes into a catalogue and world map of seismicity . Secondly, in terms of concocting a bomb, 100 ml is definitely not a magic number. In a secure military environment, I asked a highly experienced counter-terrorism artificer about this and he told me that 25 ml of certain substances would be sufficient to make a viable and powerful bomb. I do not know whether one could buy the relevant substances in the airport pharmacy, having already passed security. Later on the same day I watched a dummy human being blown to tiny pieces by 150 grams of plastic explosive, an experience that was definitely food for thought Fig. .Fig. 3PlThis example underlines the fact that there is seldom any attempt to evaluate the efficiency and effectiveness of counter-terrorism measures  states that “The City of Venice joined the [Safe Cities] Campaign as a role model for cultural heritage protection and climate change adaptation” UNISDR , p. 1. IHere is another example of how evidence can be ignored. In 2016 the government of the United Kingdom made a policy that junior hospital doctors must work more hours for lower salaries at weekends. The rationale offered was that the quality of healthcare was lower at weekends and as a result more people were dying in hospitals on Saturdays and Sundays. In reality, a study , mutation rate, asymptomatic transmission potential, case-fatality rate, whether there would be several waves, its impact , the acquisition of individual and “herd” immunity, how long immunity might last, the relationship of the disease to environmental factors, the efficacy of personal protective equipment, and what prospects existed for developing a functional vaccine against the disease. The response to this involved learning that was virtually unprecedented in its scope and rapidity. It also involved persistent controversy about almost all aspects of the disease and its actual or potential impact. None of this was helpful to people who were forced by circumstance to make operational decisions. Yet despite this uncertainty, in most cases, there was enough of a scientific consensus to assist them—but was the response fair and rational or merely politically polarized  stated the abductive heuristic Lastly, examples described in this commentary illustrate the fact that evidence alone does not “shame” policymakers into adopting a better, more objective approach. They are perfectly at liberty to use evidence selectively, or ignore it altogether.Hence, we need an evidence-based investigation of exactly how and why policymakers ignore or manipulate the evidence.