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.

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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 …

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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).

The ORACLE II study published in 2001 compared use of amoxicillin-clavulanate (co-amoxiclav) and/or erythromycin, with placebo in women with spontaneous preterm labor (SPL) and intact membranes who had no clinical signs of infection, to determine whether these antibiotics could prevent or eliminate perinatal infections presumed to have a causative role in SPL. Neither drug produced any improvement in neonatal mortality or morbidity. The present study, the ORACLE Children Study II (OCS II), assessed long-term outcomes for 4473 children age 7 years, born in the United Kingdom to 4221 women enrolled in the original ORACLE II trial. The mothers completed a detailed structured questionnaire to assess the health status of the children. The primary outcome was the overall level of functional impairment (mild, moderate, or severe). Results from national curriculum tests assessed the education outcome. Follow-up data was obtained for 3196 of the 4473 children (71%). Compared to mothers who had received no erythromycin, more children born to mothers who had received any erythromycin (with or without co-amoxiclav) had any functional impairment: erythromycin (658 [42.3%] of 1554 children) versus no erythromycin (574 [38.3%] of 1498); odds ratio (OR) 1.18, 95% confidence interval (CI) 1.02-1.37. In contrast, there was no difference in the proportion of children whose mothers had received co-amoxiclav (with or without erythromycin) and those whose mothers had not received co-amoxiclav. More children whose mothers had received any erythromycin presented with bowel disorders. A higher proportion of children whose mothers had received either antibiotic developed cerebral palsy compared to those born to mothers who had not received these antibiotics: erythromycin (53 [3.3%] of 1611) versus no erythromycin (27 [1.7%] of 1562), OR 1.93, 95% CI 1.21-3.09; and co-amoxiclav (50 [3.2%] of 1587) versus no co-amoxiclav (30 [1.9%] of 1586), OR 1.69, 95% CI 1.07-2.67. With these two exceptions, neither antibiotic had effects on other medical conditions, or on the number of deaths, behavior, or educational attainment. The investigators conclude that these findings support the viewpoint that antibiotics are not advisable in SPL without clinical signs of infection.

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Childhood Outcomes After Prescription of Antibiotics to Pregnant Women With Spontaneous Preterm Labour : 7-Year Follow-Up of the ORACLE II Trial

The National Sentinel Caesarean Section Audit.

Jennifer Hollowell, David Puddicombe, Rachel Rowe, Louise Linsell, Pollyanna Hardy, Mary Stewart, 2 3 Maggie Redshaw, Mary Newburn, Christine McCourt, Jane Sandall, Alison Macfarlane, Louise Silverton, 6 and Peter Brocklehurst 1 7 on behalf of the Birthplace in England Collaborative Group 1 National Perinatal Epidemiology Unit, University of Oxford 2 Chelsea and Westminster Healthcare NHS Trust King‟s College London 4 NCT 5 City University, London 6 Royal College of Midwives 7 Institute for Women‟s Health, UCL

The Birthplace national prospective cohort study: perinatal and maternal outcomes by planned place of birth Birthplace in England research programme.

BACKGROUND: The recommendation for enteral iodide intake for preterm infants is 30 to 40 μg/kg per day and 1 μg/kg per day for parenteral intake. Preterm infants are vulnerable to iodide insufficiency and thyroid dysfunction. The hypothesis tested whether, compared with placebo, iodide supplementation of preterm infants improves neurodevelopment. METHODS: A randomized controlled trial of iodide supplementation versus placebo in infants RESULTS: One thousand two hundred seventy-three infants (637 intervention, 636 placebo) were recruited from 21 UK neonatal units. One hundred thirty-one infants died, and neurodevelopmental assessments were undertaken in 498 iodide and 499 placebo-supplemented infants. There were no significant differences between the intervention and placebo groups in the primary outcome: mean difference cognitive score, −0.34, 95% confidence interval (CI) −2.57 to 1.89; motor composite score, 0.21, 95% CI −2.23 to 2.65; and language composite score, −0.05, 95% CI −2.48 to 2.39. There was evidence of weak interaction between iodide supplementation and hypothyroxinemic status in the language composite score and 1 subtest score. CONCLUSIONS: Overall iodide supplementation provided no benefit to neurodevelopment measured at 2 years of age.

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Supplemental Iodide for Preterm Infants and Developmental Outcomes at 2 Years: an RCT

Preterm delivery is defined as delivery before the 37th completed week of pregnancy, and in 1996in Scotland 84% of neonatal deaths of normally formed infants were associated with preterm delivery.1 The aetiology of preterm delivery is poorly understood, though recent evidence suggests that infection may be implicated in a substantial proportion of cases.2 The part that infection plays in the development of preterm labour or preterm, pre-labour rupture of membranes leading to preterm delivery has been the focus of much research in recent years.

One element of this work has been the finding of a strong association between the presence of bacterial vaginosis and preterm delivery. Bacterial vaginosis is a common infection of the female genital tract, caused by heavy concentrations of a mixed group of organisms, including Gardnerella vaginalis , Mycoplasma hominis , and anaerobes including curved rods and Mobiluncus species. Many of these organisms are present in small numbers in the vagina normally. Symptomatic infection is characterised by a grey vaginal discharge with a …

https://www.bmj.com/content/bmj/318/7183/548.full.pdf

Peter Brocklehurst

Papers

Childhood Outcomes After Prescription of Antibiotics to Pregnant Women With Spontaneous Preterm Labour : 7-Year Follow-Up of the ORACLE II Trial

The National Sentinel Caesarean Section Audit.

The Birthplace national prospective cohort study: perinatal and maternal outcomes by planned place of birth Birthplace in England research programme.

Supplemental Iodide for Preterm Infants and Developmental Outcomes at 2 Years: an RCT

Infection and preterm delivery : There is not yet enough evidence that antibiotics help