Objective:To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008.Design:A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at ke

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7–9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a Pao
 2/Fio
 2 ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a Pao
 2/Fi
 o
 2 180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5–10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven “absolute”’ adrenal insufficiency (2C). Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

/pdf/surviving-sepsis-campaign-international-guidelines-for-229kg8suph.pdf

Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012

SUMMARY The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced extraordinary complexity into the treatment of HIV-infected persons. In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for the clinical management of HIV-infected adults and adolescents. This report recommends that care should be supervised by an expert, and makes recommendations for laboratory monitoring including plasma HIV RNA, CD4 cell counts and HIV drug resistance testing. The report also provides guidelines for antiretroviral therapy, including when to start treatment, what drugs to initiate, when to change therapy, and therapeutic options when changing therapy. Special considerations are provided for adolescents and pregnant women. As with treatment of other chronic conditions, therapeutic decisions require a mutual understanding between the patient and the health care provider regarding the benefits and risks of treatment. Antiretroviral regimens are complex, have major side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance due to non-adherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic

/pdf/guidelines-for-the-use-of-antiretroviral-agents-in-hiv-3wuv1pwax4.pdf

Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents

Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim to assist physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are not substitutes for textbooks. The legal implications of medical guidelines have been discussed previously.

A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC web site (http://www.escardio.org/knowledge/guidelines/rules).

In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed, including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in the tables below.

The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that arise during the writing period must be notified to the ESC. The Task Force report was entirely …

/pdf/european-guidelines-on-cardiovascular-disease-prevention-in-17acj3uib4.pdf

European guidelines on cardiovascular disease prevention in clinical practice (version 2012) : the fifth joint task force of the European society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).

Background and aims The optimal target range for pulse oximeter saturation (SpO 2 ) in extremely preterm infants is unknown. BOOST-II UK is one of 5 international studies that have recently investigated this. Methods Preterm infants born before 28 weeks’ gestation were randomised within 24 h of birth to an SpO 2 target range of 85–89% or 91–95%. The intervention used masked offset oximeters and was continued until 36 weeks’ gestation. The primary outcome was a composite of death or serious neurosensory disability (SND) in survivors at age 2 corrected for prematurity, evaluated in 745 infants cared for using updated trial oximeters. A sensitivity analysis restricted to infants assessed by a Bayley III examination and a secondary analysis including a further 228 infants who were studied before the oximeters were updated were also performed. Results The primary outcome was determined for 722 (96.9%) of infants. The sensitivity analysis showed similar results. In the secondary analysis the mortality difference was 4.9% (p = 0.05). Severe visual loss did not differ between groups. Conclusions The higher SpO 2 target group had 8.5% greater survival with no increase in serious neurosensory disability. For infants born before 28 weeks’’ gestation, SpO 2 targets below 90% are not recommended.

https://adc.bmj.com/content/archdischild/99/Suppl_2/A23.1.full.pdf

O-006 Follow – Up Outcomes From The Boost-ii Uk Trial Of Oxygen Saturation Targeting In Preterm Infants

BACKGROUND
Since changes in the national guidance in 2011, prophylactic antibiotics for women undergoing caesarean section are recommended prior to skin incision, rather than after the baby's umbilical cord has been clamped. Evidence from randomised controlled trials conducted outside the UK has shown that this reduces maternal infectious morbidity; however, the prophylactic antibiotics also cross the placenta, meaning that babies are exposed to them around the time of birth. Antibiotics are known to affect the gut microbiota of the babies, but the long-term effects of exposure to high-dose broad-spectrum antibiotics around the time of birth on allergy and immune-related diseases are unknown.


OBJECTIVES
We aimed to examine whether or not in-utero exposure to antibiotics immediately prior to birth compared with no pre-incisional antibiotic exposure increases the risk of (1) asthma and (2) eczema in children born by caesarean section.


DESIGN
This was a controlled interrupted time series study.


SETTING
The study took place in primary and secondary care.


PARTICIPANTS
Children born in the UK during 2006-18 delivered by caesarean section were compared with a control cohort delivered vaginally.


INTERVENTIONS
In-utero exposure to antibiotics immediately prior to birth.


MAIN OUTCOME MEASURES
Asthma and eczema in children in the first 5 years of life. Additional secondary outcomes, including other allergy-related conditions, autoimmune diseases, infections, other immune system-related diseases and neurodevelopmental conditions, were also assessed.


DATA SOURCES
The Health Improvement Network (THIN) and the Clinical Practice Research Datalink (CPRD) primary care databases and the Hospital Episode Statistics (HES) database. Previously published linkage strategies were adapted to link anonymised data on mothers and babies in these databases. Duplicate practices contributing to both THIN and the CPRD databases were removed to create a THIN-CPRD data set.


RESULTS
In the THIN-CPRD and HES data sets, records of 515,945 and 3,945,351 mother-baby pairs were analysed, respectively. The risk of asthma was not significantly higher in children born by caesarean section exposed to pre-incision antibiotics than in children whose mothers received post-cord clamping antibiotics, with an incidence rate ratio of 0.91 (95% confidence interval 0.78 to 1.05) for diagnosis of asthma in primary care and an incidence rate ratio of 1.05 (95% confidence interval 0.99 to 1.11) for asthma resulting in a hospital admission. We also did not find an increased risk of eczema, with an incidence rate ratio of 0.98 (95% confidence interval 0.94 to1.03) and an incidence rate ratio of 0.96 (95% confidence interval 0.71 to 1.29) for diagnosis in primary care and hospital admissions, respectively.


LIMITATIONS
It was not possible to ascertain the exposure to pre-incision antibiotics at an individual level. The maximum follow-up of children was 5 years.


CONCLUSIONS
There was no evidence that the policy change from post-cord clamping to pre-incision prophylactic antibiotics for caesarean sections during 2006-18 had an impact on the incidence of asthma and eczema in early childhood in the UK.


FUTURE WORK
There is a need for further research to investigate if pre-incision antibiotics have any impact on developing asthma and other allergy and immune-related conditions in older children.


STUDY REGISTRATION
This study is registered as researchregistry3736.


FUNDING
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 30. See the NIHR Journals Library website for further project information.

Long-term impact of pre-incision antibiotics on children born by caesarean section: a longitudinal study based on UK electronic health records.

Background The traditional method of risk assessment for pre-eclampsia recommended by the National Institute for Health and Care Excellence is based on maternal factors and it recommends that high-risk women should be treated with aspirin. An alternative method of screening is based on the competing risk model, which uses Bayes’ theorem to combine maternal factors with mean arterial pressure, the uterine artery pulsatility index, serum placental growth factor and pregnancy-associated plasma protein-A at 11–13 weeks’ gestation. Objective The primary aim was to compare the performance of screening by risks obtained using the competing risk model with risk assessment using the National Institute for Health and Care Excellence guidelines. Design This was a prospective multicentre observational study. Setting The setting was seven NHS maternity hospitals in England. Participants Participants were women with singleton pregnancy attending for a routine hospital visit at 11+0–13+6 weeks’ gestation between April and December 2016. Main outcome measures The performance of screening for pre-eclampsia by the competing risk model was compared with the National Institute for Health and Care Excellence method. Relative reductions in risk with aspirin prophylaxis of 30% and 60% were assumed for all pre-eclampsia and preterm pre-eclampsia, respectively. The primary comparison was the detection rate of the National Institute for Health and Care Excellence method with the detection rate of a mini-combined test (including maternal factors, mean arterial pressure and pregnancy-associated plasma protein-A) in the prediction of all pre-eclampsia for the same screen-positive rate determined by the National Institute for Health and Care Excellence method. Results In 473 (2.8%) of the 16,747 pregnancies there was development of pre-eclampsia, including 142 (0.8%) women with preterm pre-eclampsia. The screen-positive rate by the National Institute for Health and Care Excellence method was 10.3%. For all pre-eclampsia, the false-positive and detection rates by the National Institute for Health and Care Excellence method were 9.7% and 31.6%, respectively. For preterm pre-eclampsia, the false-positive and detection rates were 10.0% and 42.8%, respectively. Compliance with the National Institute for Health and Care Excellence recommendation that high-risk women should be treated with aspirin from the first trimester was 23%. For the same screen-positive rate, the detection rate of the mini-combined test for all pre-eclampsia was 42.8%, which was superior to that of the National Institute for Health and Care Excellence method by 11.2% (95% confidence interval 6.9% to 15.6%). The increase in detection for the same screen-positive rate was accompanied by a reduction in false-positive rate of 0.3%. For the same screen-positive rate as National Institute for Health and Care Excellence, the detection rate for preterm pre-eclampsia by combining maternal factors, mean arterial pressure and placental growth factor was 67.3% compared with 44.1% with the National Institute for Health and Care Excellence method. With the addition of the uterine artery pulsatility index, the detection rate was 78.6%. This was higher than that of the National Institute for Health and Care Excellence method by 35.5% (95% confidence interval 25.2% to 45.8%). Calibration of risks for pre-eclampsia was generally good, with the calibration slope very close to 1.0. The feasibility of incorporating a new biomarker was demonstrated. However, the addition of inhibin A to the full combined test did not improve the detection rates for all pre-eclampsia and preterm pre-eclampsia (61% and 80%, respectively). The same screening model for preterm pre-eclampsia by a combination of maternal factors, mean arterial pressure, the uterine artery pulsatility index and placental growth factor achieved detection rates of 45.8% and 56.3%, respectively, for preterm small for gestational age and early small for gestational age neonates. Limitation The study did not include a health economic assessment. Conclusion The findings suggest that performance of screening for pre-eclampsia provided by a combination of maternal factors and biomarkers is superior to that achieved by current National Institute for Health and Care Excellence guidelines. Future work Future work is required to identify potential biomarkers for further improvement of the competing risk model and to carry out a health economic assessment. Trial registration Current Controlled Trials ISRCTN83611527. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 8. See the NIHR Journals Library website for further project information.

https://njl-admin.nihr.ac.uk/document/download/2034926

Mini-combined test compared with NICE guidelines for early risk-assessment for pre-eclampsia: the SPREE diagnostic accuracy study

Genital herpes infection remains a difficult problem to manage during pregnancy. The natural history of the infection during pregnancy is not well understood and potential management strategies remain unevaluated. For example the risk of mother-to-child transmission in women with recurrent genital herpes lesions at the time of vaginal delivery is still unknown. We do not know whether delivery by caesarean section decreases this risk and yet it is the most widely used intervention in this situation. We are only just beginning to understand the epidemiology of asymptomatic infection and the risk that asymptomatic viral shedding may pose to the newborn. In addition, new methods of diagnosis and new strategies for management are regularly being proposed with little formal evaluation of their effectiveness in the clinical setting.This article aims to review current knowledge applicable to the clinical situation and suggest how our knowledge and management of this problem may be improved in the future.

Peter Brocklehurst

Papers

O-006 Follow – Up Outcomes From The Boost-ii Uk Trial Of Oxygen Saturation Targeting In Preterm Infants

Long-term impact of pre-incision antibiotics on children born by caesarean section: a longitudinal study based on UK electronic health records.

Mini-combined test compared with NICE guidelines for early risk-assessment for pre-eclampsia: the SPREE diagnostic accuracy study

Genital herpes infection in pregnancy

Life Study Pregnancy Component: 6 month visit, Mother questionnaire