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).

Objective To estimate the incidence and describe the risk factors, management and outcomes of placenta accreta/increta/percreta. Methods A national population-based case-control study was undertaken using the UK Obstetric Surveillance System between May 2010-April 2011. Participants comprised 134 women with placenta accreta/increta/percreta and 258 controls. Results The estimated incidence of placenta accreta/increta/percreta was 1.7 per 10,000 maternities (95%CI 1.4-2.0). Older women had raised odds of having placenta accreta/increta/percreta (aOR 3.3, 95%CI 1.4-7.6 in women 35+yrs) as did women who had a previous caesarean (aOR 14.2, 95%CI 5.5-36.5), other previous uterine surgery (aOR 2.8, 95%CI 1.1-7.7), placenta praevia diagnosed antepartum (aOR 69.5, 95%CI 17.7–273.0) and an IVF pregnancy (aOR 43.8, 95%CI 2.7–699.5). Placenta accreta/increta/percreta was suspected in 50% of women antenatally. Of the 27(20%) women who had their complete placenta left in situ, 15(56%) had a hysterectomy. Of the 107(80%) women who did not have their complete placenta left in situ, 63(59%) had a hysterectomy. Overall, 61% had other therapies to treat haemorrhage prior to hysterectomy and 5% had methotrexate used. There were no maternal deaths, but women with placenta accreta/increta/percreta were more likely to deliver preterm (aOR 16.9, 95%CI 7.5–38.1) and 70% were admitted to ITU/HDU. Conclusions Placenta accreta/increta/percreta is uncommon but associated with preterm delivery and significant maternal morbidity. This study confirms previously reported associations including with prior caesarean delivery; the association with IVF pregnancy requires confirmation in other studies. Treatment varied and further investigation of the clinical effectiveness of different management strategies is warranted.

https://fn.bmj.com/content/fetalneonatal/97/Suppl_1/A4.3.full.pdf

Placenta accreta/increta/percreta: incidence, risk factors, management and outcomes

EPIC Project: Evidence into practice: evaluating a child-centred intervention for diabetes medicine management.

Background:

Evidence from the 2009 A/H1N1 influenza pandemic demonstrated that pregnant women are particularly vulnerable to infection and at an increased risk of death. Active data collection through the UK Obstetric Surveillance System (UKOSS) about women admitted to hospital during the 2009 A/H1N1 pandemic was used to inform ongoing clinical guidance regarding the use of antiviral treatment for pregnant women and demonstrated that, in addition to an increased risk of maternal morbidity, influenza infection in pregnancy is associated with poor perinatal outcomes, including an increased risk of stillbirth and preterm birth. This evidence influenced the decision to offer routine influenza immunisation to pregnant women. Even in a non-epidemic period, pregnant women continue to die from influenza.
Objective:

To establish, and then to put into hibernation, the study mechanisms needed to mount a rapid investigation of the impact of pandemic influenza in pregnancy in the event of a newly emerging pandemic strain.
Design:

A new UKOSS cohort study was designed, based on the 2009–10 study, and following consultation with the Pandemic Flu Planning Group at the Royal College of Obstetricians and Gynaecologists and the UKOSS Steering Committee, to identify potential previously unanswered questions.
Setting:

UK maternity units.
Participants:

All pregnant women admitted to hospital with influenza in a future pandemic.
Main outcome measures:

Management of pregnant women with influenza infection, intervention rates, treatment and pregnancy outcome for both the mother and fetus.
Results:

The study was designed and approved by the UKOSS Steering Committee and then placed into hibernation for activation in the event of an influenza pandemic.
Conclusions:

Pregnant women, as a result of their changed immunological status, appear to be particularly susceptible to infection, including from influenza. The existence of the UKOSS enabled us to rapidly mount a study of pregnant women who were hospitalised with 2009 A/H1N1 influenza. Minor modifications to incorporate previously unanswered questions and our previous study enabled us to design, and then put into hibernation, a new study ready to investigate the impact and management of influenza in pregnancy, which is poised for activation in the event of a newly emerging pandemic strain. This will enable real-time data to be available on which to base rapid changes in clinical management as the as-yet-unforeseen pandemic unfolds. In the event of an influenza pandemic the study will be available to be immediately activated following expedited regulatory approvals.
Trial registration:

Current Controlled Trials ISRCTN44137563.
Funding:

The National Institute for Health Research Health Services and Delivery Research programme.

https://njl-admin.nihr.ac.uk/document/download/2003756

Planning for a cohort study to investigate the impact and management of influenza in pregnancy in a future pandemic

Risk of stillbirth after previous caesarean section.

Preterm birth is associated with significant mortality and morbidity for mothers and babies. Women are identified as high risk for preterm birth based on either previous medical/pregnancy history or on ultrasound assessment of the cervix. Women identified as high risk can be offered a cervical cerclage (a purse string stitch) around the cervix (neck of the womb) to reduce the risk of preterm birth. In women who have a cervical cerclage, the procedure can be performed using either a monofilament (single-stranded) or braided (woven) suture material. Both suture materials are routinely used for cervical cerclage and there is uncertainty as to which is superior. A multicentre, open, randomised controlled superiority trial of 2050 women presenting at obstetric units, deemed to be at risk of preterm birth and already scheduled to have a cervical cerclage as part of their standard care. Inclusion criteria include singleton pregnancies and an indication for cervical cerclage for either a history of three or more previous mid-trimester losses or premature births (≤ 28 weeks), insertion of cervical sutures in previous pregnancies, a history of mid trimester loss or premature birth with a (current) shortened (≤ 25 mm) cervix, or women whom clinicians deem to be at risk of preterm birth either by history or the results of an ultrasound scan. Exclusion criteria include women who have taken part in C-STICH previously, are aged less than 18 years old at the time of presentation, require a rescue cerclage, and are unwilling or unable to give informed consent and in whom a cerclage will be placed by any route other than vaginally (e.g. via an abdominal route). Following informed consent, women are randomised on a 1:1 basis to either monofilament or braided suture, by minimisation. The primary outcome is pregnancy loss (miscarriage and perinatal mortality, including any stillbirth or neonatal death in the first week of life), and secondary outcomes include the core outcome set for preterm birth trials. Optimising established interventions to prevent preterm birth is important in reducing perinatal mortality rates. ISRCTN 15373349
 . Registered before recruitment on 03 December 2014 prior to first recruit.

/pdf/c-stich-cerclage-suture-type-for-an-insufficient-cervix-and-25zi44fohh.pdf

Peter Brocklehurst

Papers

Placenta accreta/increta/percreta: incidence, risk factors, management and outcomes

EPIC Project: Evidence into practice: evaluating a child-centred intervention for diabetes medicine management.

Planning for a cohort study to investigate the impact and management of influenza in pregnancy in a future pandemic

Risk of stillbirth after previous caesarean section.

C-STICH: Cerclage Suture Type for an Insufficient Cervix and its effect on Health outcomes-a multicentre randomised controlled trial.