Postpartum hemorrhage (PPH) is a major cause of maternal mortality and morbidity worldwide. Several recent publications have noted an increasing trend in incidence over time. The international PPH ...collaboration was convened to explore the observed trends and to set out actions to address the factors identified.
We reviewed available data sources on the incidence of PPH over time in Australia, Belgium, Canada, France, the United Kingdom and the USA. Where information was available, the incidence of PPH was stratified by cause.
We observed an increasing trend in PPH, using heterogeneous definitions, in Australia, Canada, the UK and the USA. The observed increase in PPH in Australia, Canada and the USA was limited solely to immediate/atonic PPH. We noted increasing rates of severe adverse outcomes due to hemorrhage in Australia, Canada, the UK and the USA.
Key Recommendations 1. Future revisions of the International Classification of Diseases should include separate codes for atonic PPH and PPH immediately following childbirth that is due to other causes. Also, additional codes are required for placenta accreta/percreta/increta. 2. Definitions of PPH should be unified; further research is required to investigate how definitions are applied in practice to the coding of data. 3. Additional improvement in the collection of data concerning PPH is required, specifically including a measure of severity. 4. Further research is required to determine whether an increased rate of reported PPH is also observed in other countries, and to further investigate potential risk factors including increased duration of labor, obesity and changes in second and third stage management practice. 5. Training should be provided to all staff involved in maternity care concerning assessment of blood loss and the monitoring of women after childbirth. This is key to reducing the severity of PPH and preventing any adverse outcomes. 6. Clinicians should be more vigilant given the possibility that the frequency and severity of PPH has in fact increased. This applies particularly to small hospitals with relatively few deliveries where management protocols may not be defined adequately and drugs or equipment may not be on hand to deal with unexpected severe PPH.
Recent developments in MALDI have enabled direct detection of lipids as intact molecular species present within cellular membranes. Abundant lipid-related ions are produced from the direct analysis ...of thin tissue slices when sequential spectra are acquired across a tissue surface that has been coated with a MALDI matrix. The lipid-derived ions can often be distinguished from other biomolecules because of the significant mass defect that these ions present due to the large number of covalently bound hydrogen atoms in hydrophobic molecules such as lipids. Collisional activation of the molecular ions can be used to determine the lipid family and often structurally define the molecular species. Specific examples in the detection of phospholipids, sphingolipids, and glycerolipids are presented with images of mouse brain and kidney tissue slices. Regional distribution of many different lipid molecular species and Na+ and K+ attachment ions often define anatomical regions within the tissues.
Individuals suffering from obstructive sleep apnea (OSA) are at increased risk for systemic hypertension. The importance of a healthy gut microbiota, and detriment of a dysbiotic microbiota, on host ...physiology is becoming increasingly evident. We tested the hypothesis that gut dysbiosis contributes to hypertension observed with OSA. OSA was modeled in rats by inflating a tracheal balloon during the sleep cycle (10-s inflations, 60 per hour). On normal chow diet, OSA had no effect on blood pressure; however, in rats fed a high-fat diet, blood pressure increased 24 and 29 mm Hg after 7 and 14 days of OSA, respectively (P<0.05 each). Bacterial community characterization was performed on fecal pellets isolated before and after 14 days of OSA in chow and high-fat fed rats. High-fat diet and OSA led to significant alterations of the gut microbiota, including decreases in bacterial taxa known to produce the short chain fatty acid butyrate (P<0.05). Finally, transplant of dysbiotic cecal contents from hypertensive OSA rats on high-fat diet into OSA recipient rats on normal chow diet (shown to be normotensive) resulted in hypertension similar to that of the donor (increased 14 and 32 mm Hg after 7 and 14 days of OSA, respectively; P<0.05). These studies demonstrate a causal relationship between gut dysbiosis and hypertension, and suggest that manipulation of the microbiota may be a viable treatment for OSA-induced, and possibly other forms of, hypertension.
To estimate the prevalence of epilepsy in children with Autism Spectrum Disorder (ASD) and to determine the demographic and clinical characteristics of children with ASD and epilepsy in a large ...patient population.
Cross-sectional study using four samples of children with ASD for a total of 5,815 participants with ASD. The prevalence of epilepsy was estimated from a population-based sample. Children with and without epilepsy were compared on demographic and clinical characteristics. Multivariate logistic regression was used to examine the association between demographic and clinical characteristics and epilepsy.
The average prevalence of epilepsy in children with ASD 2-17 years was 12.5%; among children aged 13 years and older, 26% had epilepsy. Epilepsy was associated with older age, lower cognitive ability, poorer adaptive and language functioning, a history of developmental regression and more severe ASD symptoms. The association between epilepsy and the majority of these characteristics appears to be driven by the lower IQ of participants with epilepsy. In a multivariate regression model, only age and cognitive ability were independently associated with epilepsy. Children age 10 or older had 2.35 times the odds of being diagnosed with epilepsy (p<.001) and for a one standard deviation increase in IQ, the odds of having epilepsy decreased by 47% (p<.001).
This is among the largest studies to date of patients with ASD and co-occurring epilepsy. Based on a representative sample of children with ASD, the average prevalence of epilepsy is approximately 12% and reaches 26% by adolescence. Independent associations were found between epilepsy and older age and lower cognitive ability. Other risk factors, such as poor language and developmental regression, are not associated with epilepsy after controlling for IQ. These findings can help guide prognosis and alert clinicians to patients with ASD who are at increased risk for epilepsy.
Disruption of the gut microbiota, termed gut dysbiosis, has been described in animal models of hypertension and hypertensive patients. We have shown that gut dysbiosis plays a causal role in the ...development of hypertension in a rat model of obstructive sleep apnea (OSA). Functional analysis of the dysbiotic microbiota in OSA demonstrates a loss of short chain fatty acid–producing bacteria. However, measurements of short chain fatty acid concentrations and testing of their role in blood pressure regulation are lacking. We hypothesized that reduced short chain fatty acids in the gut are responsible for OSA-induced hypertension. OSA significantly increased systolic blood pressure at 7 and 14 days (P<0.05), an effect that was abolished by the probiotic Clostridium butyricum or the prebiotic Hylon VII. The 16S rRNA analysis identified several short chain fatty acid–producing bacteria that were significantly increased by Cbutyricum and Hylon treatment. Acetate concentration in the cecum was decreased by 48% after OSA (P<0.05), an effect that was prevented by Cbutyricum and Hylon. Cbutyricum and Hylon reduced OSA-induced dysbiosis, epithelial goblet cell loss, mucus barrier thinning, and activation of brain microglia (P<0.05 for each). To examine the role of acetate in OSA-induced hypertension, we chronically infused acetate into the cecum during 2 weeks of sham or OSA. Restoring cecal acetate concentration prevented OSA-induced gut inflammation and hypertension (P<0.05). These studies identify acetate as a key player in OSA-induced hypertension. We demonstrate that various methods to increase cecal acetate concentrations are protective from the adverse effects of OSA on the microbiota, gut, brain, and blood pressure.
ACC/AHA Task Force Members Glenn N. Levine, MD, FACC, FAHA, Chair Patrick T. O’Gara, MD, MACC, FAHA, Chair-Elect Jonathan L. Halperin, MD, FACC, FAHA, Immediate Past Chair‡‡ Sana M. Al-Khatib, MD, ...MHS, FACC, FAHA Joshua A. Beckman, MD, MS, FAHA Kim K. Birtcher, PharmD, MS, AACC Biykem Bozkurt, MD, PhD, FACC, FAHA‡‡ Ralph G. Brindis, MD, MPH, MACC‡‡ Joaquin E. Cigarroa, MD, FACC Lesley H. Curtis, PhD, FAHA‡‡ Anita Deswal, MD, MPH, FACC, FAHA Lee A. Fleisher, MD, FACC, FAHA Federico Gentile, MD, FACC Samuel Gidding, MD, FAHA‡‡ Zachary D. Goldberger, MD, MSc, FACC, FAHA Mark A. Hlatky, MD, FACC, FAHA John Ikonomidis, MD, PhD, FAHA‡‡ José A. Joglar, MD, FACC, FAHA Laura Mauri, MD, MSc, FAHA‡‡ Mariann R. Piano, RN, PhD, FAHA Susan J. Pressler, PhD, RN, FAHA‡‡ Barbara Riegel, PhD, RN, FAHA‡‡ Duminda N. Wijeysundera, MD, PhD‡‡Former Task Force member; current member during the writing effort.Table of Contents Top 10 Take-Home Messages For the Management of Bradycardia and Cardiac Conduction Delaye53 Preamblee54 Introductione55 1.1.Methodology and Evidence Reviewe55 1.2.Organization of the Writing Committeee55 1.3.Document Review and Approvale55 1.4.Scope of the Guidelinee56 1.5.Class of Recommendation and Level of Evidencee56 1.6.Abbreviationse56 2. General Evaluation of Patients With Documented or Suspected Bradycardia or Conduction Disorderse61 4.1.History and Physical Examination of Patients With Documented or Suspected Bradycardia or Conduction Disorderse61 4.2.Noninvasive Evaluatione66 4.2.1.Resting ECG in Patients With Documented or Suspected Bradycardia or Conduction Disorderse66 4.2.2.Exercise Electrocardiographic Testing in Patients With Documented or Suspected Bradycardia or Conduction Disorderse66 4.2.3.Ambulatory Electrocardiography in Patients With Documented or Suspected Bradycardia or Conduction Disorderse67 4.2.4.Imaging in Patients With Documented or Suspected Bradycardia or Conduction Disorderse69 4.2.5.Laboratory Testing in Patients With Documented or Suspected Bradycardia or Conduction Disorderse70 4.2.6.Genetic Testing in Patients With Documented or Suspected Bradycardia or Conduction Disorderse71 4.2.7.Sleep Apnea Evaluation and Treatment in Patients With Documented or Suspected Bradycardia or Conduction Disorderse72 4.3. In patients with a left ventricular ejection fraction between 36% to 50% and atrioventricular block, who have an indication for permanent pacing and are expected to require ventricular pacing >40% of the time, techniques that provide more physiologic ventricular activation (e.g., cardiac resynchronization therapy, His bundle pacing) are preferred to right ventricular pacing to prevent heart failure. Because conduction system abnormalities are common after transcatheter aortic valve replacement, recommendations on postprocedure surveillance and pacemaker implantation are made in this guideline. Using the principles of shared decision-making and informed consent/refusal, patients with decision-making capacity or his/her legally defined surrogate has the right to refuse or request withdrawal of pacemaker therapy, even if the patient is pacemaker dependent, which should be considered palliative, end-of-life care, and not physician-assisted suicide.
ABSTRACT BACKGROUND The mode of delivery for women with a previous cesarean delivery remains contentious. We conducted a study comparing maternal and infant outcomes after attempted vaginal birth ...after cesarean delivery versus elective repeat cesarean delivery. METHODS We used data from the Discharge Abstract Database that includes all hospital deliveries in Canada (excluding Quebec). In our analysis, we included singleton deliveries to women between 37 and 43 weeks gestation who had a single prior cesarean delivery between April 2003 and March 2015. The primary outcomes were severe maternal morbidity and mortality, and serious neonatal morbidity and mortality. We used logistic regression to estimate adjusted rate ratios (RRs) and 95% confidence intervals (CIs). RESULTS Absolute rates of severe maternal morbidity and mortality were low but significantly higher after attempted vaginal birth after cesarean delivery compared with elective repeat cesarean delivery (10.7 v. 5.65 per 1000 deliveries, respectively; adjusted RR 1.96, 95% CI 1.76 to 2.19). Adjusted rate differences in severe maternal morbidity and mortality, and serious neonatal morbidity and mortality were small (5.42 and 7.09 per 1000 deliveries, respectively; number needed to treat 184 and 141, respectively). The association between vaginal birth after cesarean delivery, and serious neonatal morbidity and mortality showed a temporal worsening (adjusted RR 0.94, 95% CI 0.77 to 1.15 in 2003–2005; adjusted RR 2.07, 95% CI 1.83 to 2.35 in 2012–2014). INTERPRETATION Although absolute rates of adverse outcomes are low, attempted vaginal birth after cesarean delivery continues to be associated with higher relative rates of severe morbidity and mortality in mothers and infants. Temporal worsening of infant outcomes after attempted vaginal birth after cesarean delivery highlights the need for greater care in selecting candidates, and more careful monitoring of labour and delivery.
Combination programmed cell death protein 1/cytotoxic T-cell lymphocyte-4-blockade and dual BRAF/MEK inhibition have each shown significant clinical benefit in patients with
-mutant metastatic ...melanoma, leading to broad regulatory approval. Little prospective data exist to guide the choice of either initial therapy or treatment sequence in this population. This study was conducted to determine which initial treatment or treatment sequence produced the best efficacy.
In a phase III trial, patients with treatment-naive
-mutant metastatic melanoma were randomly assigned to receive either combination nivolumab/ipilimumab (arm A) or dabrafenib/trametinib (arm B) in step 1, and at disease progression were enrolled in step 2 to receive the alternate therapy, dabrafenib/trametinib (arm C) or nivolumab/ipilimumab (arm D). The primary end point was 2-year overall survival (OS). Secondary end points were 3-year OS, objective response rate, response duration, progression-free survival, crossover feasibility, and safety.
A total of 265 patients were enrolled, with 73 going onto step 2 (27 in arm C and 46 in arm D). The study was stopped early by the independent Data Safety Monitoring Committee because of a clinically significant end point being achieved. The 2-year OS for those starting on arm A was 71.8% (95% CI, 62.5 to 79.1) and arm B 51.5% (95% CI, 41.7 to 60.4; log-rank
= .010). Step 1 progression-free survival favored arm A (
= .054). Objective response rates were arm A: 46.0%; arm B: 43.0%; arm C: 47.8%; and arm D: 29.6%. Median duration of response was not reached for arm A and 12.7 months for arm B (
< .001). Crossover occurred in 52% of patients with documented disease progression. Grade ≥ 3 toxicities occurred with similar frequency between arms, and regimen toxicity profiles were as anticipated.
Combination nivolumab/ipilimumab followed by BRAF and MEK inhibitor therapy, if necessary, should be the preferred treatment sequence for a large majority of patients.
The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain recently sponsored the development of evidence-based guidelines for the pharmacological treatment of ...neuropathic pain. Tricyclic antidepressants, dual reuptake inhibitors of serotonin and norepinephrine, calcium channel α2 -δ ligands (ie, gabapentin and pregabalin), and topical lidocaine were recommended as first-line treatment options on the basis of the results of randomized clinical trials. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in certain clinical circumstances. Results of several recent clinical trials have become available since the development of these guidelines. These studies have examined botulinum toxin, high-concentration capsaicin patch, lacosamide, selective serotonin reuptake inhibitors, and combination therapies in various neuropathic pain conditions. The increasing number of negative clinical trials of pharmacological treatments for neuropathic pain and ambiguities in the interpretation of these negative trials must also be considered in developing treatment guidelines. The objectives of the current article are to review the Neuropathic Pain Special Interest Group guidelines for the pharmacological management of neuropathic pain and to provide a brief overview of these recent studies.
PDF
