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1.  Diagnostic Accuracy of Ultrasound in Determining the Cause of Bilious Vomiting in Neonates 
Iranian Journal of Radiology  2012;9(4):190-194.
Background
Plain radiography and contrast radiologic studies are traditionally the main options in evaluating neonates presenting with bilious vomiting. While ultrasonography (US) is more available, its diagnostic accuracy is in question.
Objectives
The purpose of this study is to determine the diagnostic accuracy of US in evaluating these patients with bilious vomiting.
Patients and Methods
All neonates with bilious vomiting or bilious nasogastric tube drainage presented to a children’s hospital in a 1.5-year period were included. US were performed in all patients. The results were compared with clinical and radiological data and the final diagnosis. We used chi-square and Fisher’s exact tests for analysis.
Results
The cause of bilious vomiting for 18 of the 23 included patients was surgical. All patients labeled as surgical candidates by US ended in surgery [positive predictive value (PPV) = 100%], while only 50% of the patients with inconclusive US were operated [negative predictive value (NPV) = 50%, Confidence Interval (CI) 95%: 29%-71%]. The sensitivity and specificity of US in diagnosing intestinal atresia (n = 9) was 89% [CI 95%: (68% - 100%)] and 100%. In cases with malrotation (n = 4) and midgut volvulus (n = 2), sonographic diagnosis was in concordance with final surgical diagnosis.
Conclusion
This study suggested that in cases in which US makes a certain diagnosis, its accuracy eliminates the need for further diagnostic tests, but if it is inconclusive, further radiological contrast studies should be tried to make the final diagnosis.
doi:10.5812/iranjradiol.8465
PMCID: PMC3569550  PMID: 23407700
Ultrasonography; Vomiting; Infant, Newborn; Bilious
2.  Pediatric Gastric Volvulus: Diagnostic and Clinical Approach 
Gastric volvulus is a significant, rare cause of non-bilious vomiting and consists of a pathological rotation of the stomach of more than 180° around the axis without obstruction of the gastrointestinal tract. A definitive diagnosis is made with upper radiological gastrointestinal studies. Treatment may be conservative or surgical with anterior and fundal gastropexy in patients with ingravescent symptoms. We describe the case of a 16-month-old female admitted to our hospital for recurrent and postprandial vomiting episodes which had started at 11 months of age. A history of gastroesophageal reflux was present until 1 year of age, in association with recurrent respiratory infections. The basic metabolic panel was normal. Barium study showed stomach rotation along a horizontal plane stomach. Esophagogastroduodenoscopy showed no mucosal alterations. The diagnosis was chronic organoaxial gastric volvulus. In our patient, the surgical procedure of gastropexy, both anterior and fundal, without fundoplication was performed. She showed good improvement after surgery, with resolution of symptoms and weight gain.
doi:10.1159/000348758
PMCID: PMC3617890  PMID: 23626505
Postprandial vomiting; Chronic gastric volvulus; Anterior; fundal gastropexy
3.  Acute gastric volvulus: an uncommon complication of a hiatus hernia 
BMJ Case Reports  2011;2011:bcr0920114753.
An 80-year-old male patient with a history of a hiatus hernia presented with acute abdominal pain and vomiting. CT of his abdomen revealed extraluminal free gas consistent with a perforation. He had a large hiatus hernia. The subdiaphragmatic portion of the stomach was distended and adopted a more transverse lie. The radiological findings were in keeping with acute gastric volvulus with secondary ischaemic complications. Acute gastric volvulus is an abnormal rotation of the stomach resulting in complete obstruction. It is a surgical emergency and does not always present in its classical form. Clinicians should be mindful of this diagnosis in patients presenting with an acute surgical abdomen, especially if the presentation is non-specific, as delays in diagnosis are associated with significant morbidity and mortality.
doi:10.1136/bcr.09.2011.4753
PMCID: PMC3207776  PMID: 22675018
4.  A personalized care plan in chronic care: implementation and evaluation 
Purpose
Implementation and evaluation of a personalized care plan for approximately 350 people with (an increased risk of) cardiovascular disease in ten general practices in the Netherlands.
Context
The ‘Healthy Vessels’ (‘Vitale Vaten’) care standard of 2009 describes the optimum care for people with (an increased risk of) cardiovascular disease and is based on the Chronic Care Model. New: working with a personalized care plan, with detailed attention for the promotion of self-management and shared decision-making (SDM). This requires patients to adopt a more active attitude, with a more coaching role from care providers. Vilans has developed the personalized care plan for cardiovascular disease (the booklet ‘Zorgplan Vitale Vaten’) and the personalized care plan for diabetes and for COPD in 2011. In 2011 Vilans also started with the development of a general care plan for patients with multi morbidity diseases.
Data sources
Patients: quantitative survey with a written questionnaire sent to approximately 75 patients. Baseline and end points for 40 patients, plus in-depth interviews with eight patients.
Care providers
Quantitative survey with a written questionnaire sent to 45 care providers. Baseline and end points for 22 care providers, plus in-depth interviews with 10 care providers.
Case description
The personalized care plan is produced by a shared decision-making process and consists of:
A prioritised list of the patient’s SMART objectives
A personalized plan for achieving those objectives
Agreements concerning what the patient will do himself/herself and the support or advice needed
Agreements concerning contact to review the progress (how and when)
The patient or the care provider notes the plan in the patient’s booklet (the ‘Zorgplan Vitale Vaten’=‘Healthy Vessels Care Plan’). This booklet also contains information about the risk factors for cardiovascular disease, the importance of the patient adopting an active role, measurement values, medication and the patient’s care providers.
Advisers from Vilans, the knowledge centre for long-term care in the Netherlands, provide participating organisations guidance for the implementation of the personalized care plan with: work conferences, supporting products and monthly support phone-calls or e-mails.
The project consists of the following phases:
Jan 2010 to Jun 2010: development of materials
Jun 2010 to Oct 2011: implementation and evaluation in ten general practices
Nov 2011 to Feb 2012: project completion and reporting
The results will be available in February 2012
The study questions in this project are:
What effects does the personalized care plan have on the level of self-management of the patients?
What effects does the personalized care plan have on professionals in a multidisciplinary team?
Do the effects also apply to ethnic minority patients and patients with a low socio-economic status?
(Preliminary) conclusions:
Self-management/Shared Decision Making is difficult to implement. Regular feedback and joint learning are needed.
It is helpful when agreements between the patient and the care provider are made concrete: writing things down makes a difference.
Variable response from patients: ranging from ‘good to know you have something to fall back on’ to ‘the idea of writing down personal objectives makes me feel a bit nervous’.
The personalized care plan does not seem suitable for all, in particular not for the elderly, for those of low socio-economic status, and for ethnic minorities.
Discussion
Health care professionals are used to take care of patients with chronic diseases. They are very willing to help and give patients some advice about how they can prevent a chronic disease or have a good life with a chronic disease. During the conferences and phone calls we have with them, we see that the focus is more on caring instead of sharing and self-management. It frustrates professionals when patients do not behave the way they tell them to. They do not know how to handle or turn the conversation into self-management and rather fall back in their roll of caring. It seems necessary to get feedback on a regular basis so they can explore new ways of self-management support together in a multidisciplinary way.
Self-management support is more successful when professionals are working together, looking for ways to take into account the perspective and expectations of the patient as well as those of the professional. The personalized care plan can help patients and professionals exploring their new roles.
There are some relevant questions concerning personalized care plans in practice which we cannot yet answer. We would like to discuss these essential questions with the participants of INIC12. For example:
How important is it for patients to have a personalized care plan? Does it support them in making decisions concerning their health in daily life? In what way can a digital care plan provide help?
Do professionals improve their caring and communication with patients with chronic diseases when they use a personalized care plan?
Is it more successful when one professional is the central care provider for a patient?
What are good ways for integrating personalized care plans in usual care? Does it take more time in comparison to regular care?
How to create possibilities for professionals so they can regard the personalized care plan as an important topic in chronic care? We see it is difficult for a small group of patients. How to implement the personalized care plan for all the patients with a chronic disease?
What do the answers to these questions mean and does individual care planning change the health care process in such a way that self-management can flourish?
PMCID: PMC3617761
personalized care plan; self-management; vascular risk; multidisciplinary team; chronic care
5.  Intestinal malrotation with suspected cow’s milk allergy: a case report 
BMC Research Notes  2012;5:481.
Background
Intestinal malrotation is an incomplete rotation of the intestine. Failure to rotate leads to abnormalities in intestinal positioning and attachment that leave obstructing bands across the duodenum and a narrow pedicle for the midgut loop, thus making it susceptible to volvulus. One of the important differential diagnoses for malrotation is an allergy to cow’s milk. Several studies have described infants with surgical gastrointestinal diseases and cow’s milk allergy. However, to our knowledge, no study has reported infants with intestinal malrotation who have been symptomatic before surgery was performed and have been examined by allergen-specific lymphocyte stimulation test and food challenge tests with long-term follow-up.
Case presentation
The patient was a Japanese male born at 39 weeks of gestation. He was breast-fed and received commercial cow’s milk supplementation starting the day of birth and was admitted to our hospital at 6 days of age due to bilious vomiting. Plain abdominal radiography showed a paucity of gas in the distal bowel. Because we demonstrated malpositioning of the intestine by barium enema, we repositioned the bowel in a normal position by laparotomy. The patient was re-started on only breast milk 2 days post surgery because we suspected the presence of a cow’s milk allergy, and the results of an allergen-specific lymphocyte stimulation test showed a marked increase in lymphocyte response to kappa-casein. At 5 months of age, the patient was subjected to a cow’s milk challenge test. After the patient began feeding on cow’s milk, he had no symptoms and his laboratory investigations showed no abnormality. In addition, because the patient showed good weight gain and no symptoms with increased cow’s milk intake after discharge, we concluded that the present case was not the result of a cow’s milk allergy. At 1 year, the patient showed favorable growth and development, and serum allergy investigations revealed no reaction to cow’s milk.
Conclusion
When physicians encounter infants with surgical gastrointestinal disease, including intestinal malrotation, they should consider cow’s milk allergy as a differential diagnosis or complication and should utilize food challenge tests for a definitive diagnosis.
doi:10.1186/1756-0500-5-481
PMCID: PMC3490812  PMID: 22943656
Allergen-specific lymphocyte stimulation test; Cow’s milk allergy; Food challenge test; Infant; Intestinal malrotation
6.  Gastric volvulus and associated gastro-oesophageal reflux. 
Archives of Disease in Childhood  1995;73(5):462-464.
Between 1984 and 1994, 10 neurologically normal children between 2 and 24 months were diagnosed as having gastric volvulus with associated gastro-oesophageal reflux (GOR). The common features at presentation were episodic colicky abdominal pain, non-bilious vomiting, upper abdominal distension, haematemesis, and failure to thrive. Anterior gastropexy and conservative management of GOR was curative.
Images
PMCID: PMC1511387  PMID: 8554369
7.  Congenital Hemidiaphragmatic Agenesis Presenting as Reversible Mesenteroaxial Gastric Volvulus and Diaphragmatic Hernia: A Case Report 
Journal of Korean Medical Science  2009;24(3):517-519.
A 70-yr-old woman complained of left sided chest pain and non-bilious vomiting for four days after taking a gastric bloating agent for an upper gastrointestinal study. The chest radiography revealed gastric air-fluid levels and bowel loops in the left thoracic cavity. An emergency thoracotomy was performed. The abdominal organs (stomach, spleen, splenic flexure of the colon) were in the left thorax and the entire left hemidiaphragm was absent. There were no diaphragmatic remnants visible for reconstruction of the left diaphragm. We provided warm saline irrigation and performed a left lower lobe adhesiotomy. Thirteen days after surgery, the chest radiography showed improvement in the herniation but mild haziness remained at the left lower lung field. Here we present the oldest case of congenital diaphragmatic agenesis presenting with transient gastric volvulus and diaphragmatic hernia.
doi:10.3346/jkms.2009.24.3.517
PMCID: PMC2698203  PMID: 19543520
Congenital Hemidiaphragmatic Agenesis; Mesenteroaxial Gastric Volvulus; Hernia, Diaphragmatic; Spontaneous Resolution
8.  Successful Interruption of Transmission of Onchocerca volvulus in the Escuintla-Guatemala Focus, Guatemala 
Background
Elimination of onchocerciasis (river blindness) through mass administration of ivermectin in the six countries in Latin America where it is endemic is considered feasible due to the relatively small size and geographic isolation of endemic foci. We evaluated whether transmission of onchocerciasis has been interrupted in the endemic focus of Escuintla-Guatemala in Guatemala, based on World Health Organization criteria for the certification of elimination of onchocerciasis.
Methodology/Principal Findings
We conducted evaluations of ocular morbidity and past exposure to Onchocerca volvulus in the human population, while potential vectors (Simulium ochraceum) were captured and tested for O. volvulus DNA; all of the evaluations were carried out in potentially endemic communities (PEC; those with a history of actual or suspected transmission or those currently under semiannual mass treatment with ivermectin) within the focus. The prevalence of microfilariae in the anterior segment of the eye in 329 individuals (≥7 years old, resident in the PEC for at least 5 years) was 0% (one-sided 95% confidence interval [CI] 0–0.9%). The prevalence of antibodies to a recombinant O. volvulus antigen (Ov-16) in 6,432 school children (aged 6 to 12 years old) was 0% (one-sided 95% IC 0–0.05%). Out of a total of 14,099 S. ochraceum tested for O. volvulus DNA, none was positive (95% CI 0–0.01%). The seasonal transmission potential was, therefore, 0 infective stage larvae per person per season.
Conclusions/Significance
Based on these evaluations, transmission of onchocerciasis in the Escuintla-Guatemala focus has been successfully interrupted. Although this is the second onchocerciasis focus in Latin America to have demonstrated interruption of transmission, it is the first focus with a well-documented history of intense transmission to have eliminated O. volvulus.
Author Summary
Brought to the Americas from Africa by the slave trade, onchocerciasis is present in six countries in Latin America. The disease is caused by a round worm and is transmitted to humans by the bite of an infected black fly. Once in a human, the adult worms produce larvae that circulate through the body, causing itching or even blindness. Ivermectin, a drug that kills the larvae, is delivered by public health authorities in countries where the disease is present. If the larvae are killed, then the disease cannot be transmitted to more people. People living in the Escuintla-Guatemala focus, a region in Guatemala where the disease was common, have been taking ivermectin for many years. The Ministry of Health of Guatemala believes that onchocerciasis is no longer being transmitted in the area. To prove that there is no more transmission of the disease, the authors examined the eyes of residents of the area to see if they could find any evidence of the worms. They also conducted analyses of blood in school children to see if they had ever been exposed to the worm, and they caught thousands of black flies and tested them to see if they were infected. These evaluations found no evidence of transmission of the disease in the Escuintla-Guatemala focus. As a result, local public health authorities can stop giving ivermectin and invest their human resources in other important diseases.
doi:10.1371/journal.pntd.0000404
PMCID: PMC2656640  PMID: 19333366
9.  Intestinal ascariasis at pediatric emergency room in a developed country 
World Journal of Gastroenterology : WJG  2014;20(38):14058-14062.
Ascaris lumbricoides infection is rare among children in developed countries. Although large numbers of adult Ascaris in the small intestine can cause various abdominal symptoms, this infection remains asymptomatic until the number of worms in the intestine considerably increases in most cases. Ascaris causing bilious vomiting suggesting ileus is rare, especially in developed countries. A 6-year-old boy who lived in Japan, presented with abdominal colic, bilious vomiting at the pediatric emergency room. He appeared pale, and had no abdominal distention, tenderness, palpable abdominal mass, or findings of dehydration. He experienced bilious vomiting again during a physical examination. Laboratory tests showed mild elevation of white blood cells and C-reactive protein levels. Antigens of adenovirus, rotavirus, and norovirus were not detected from his stool, and stool culture showed normal flora. Ultrasonography showed multiple, round-shaped structures within the small intestine, and a tubular structure in a longitudinal scan of the small intestine. Capsule endoscopy showed a moving worm of Ascaris in the jejunum. Intestinal ascariasis should be considered as a cause of bilious vomiting in children, even at the emergency room in industrial countries. Ultrasound examination and capsule endoscopy are useful for diagnosis of pediatric intestinal ascariasis.
doi:10.3748/wjg.v20.i38.14058
PMCID: PMC4194592  PMID: 25320546
Ascaris lumbricoides; Paralytic ileus; Capsule endoscopy; Ultrasound; Bilious vomiting
10.  Nausea and vomiting in early pregnancy 
Clinical Evidence  2009;2009:1405.
Introduction
More than half of pregnant women suffer from nausea and vomiting, which typically begins by the 4th week and disappears by the 16th week of pregnancy. The cause of nausea and vomiting in pregnancy is unknown, but may be due to the rise in human chorionic gonadotrophin concentration. In 1 in 200 women, the condition progresses to hyperemesis gravidarum, which is characterised by prolonged and severe nausea and vomiting, dehydration, and weight loss.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatment for nausea and vomiting in early pregnancy? What are the effects of treatments for hyperemesis gravidarum? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 30 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupressure; acupuncture; antihistamines; corticosteroids; corticotrophins; diazepam; dietary interventions other than ginger; domperidone; ginger; metoclopramide; ondansetron; phenothiazines; and pyridoxine (vitamin B6).
Key Points
More than half of pregnant women suffer from nausea and vomiting, which typically begins by the 4th week and disappears by the 16th week of pregnancy. The cause of nausea and vomiting in pregnancy is unknown, but may be due to the rise in human chorionic gonadotrophin concentration.In 1 in 200 women, the condition progresses to hyperemesis gravidarum, which is characterised by prolonged and severe nausea and vomiting, dehydration, and weight loss.
Ginger may reduce nausea and vomiting in pregnancy compared with placebo, although studies have given inconclusive results. Pyridoxine may be as effective as ginger in reducing nausea, although studies have given inconsistent results about reduction of vomiting.We don't know whether dietary interventions other than ginger are beneficial.
P6 acupressure may reduce nausea and vomiting compared with sham acupressure, but wristbands can be difficult to use. We don't know whether acupressure is more effective than pyridoxine at reducing nausea or vomiting.
We don't know whether acupuncture is more effective than sham acupuncture at reducing nausea and vomiting.
Antihistamines may reduce nausea and vomiting compared with placebo. The antihistamine dimenhydrinate may be as effective as ginger at improving nausea at 7 days, although it seems more effective at reducing vomiting episodes in the first 2 days.
We don't know whether phenothiazines, metoclopramide, or domperidone reduce nausea or vomiting.
Acupressure may be more effective at reducing vomiting episodes in women with hyperemesis gravidarum compared with placebo or control (intravenous fluid therapy).
We don't know whether acupuncture, intramuscular corticotrophin, corticosteroids, diazepam, ginger, metoclopramide, ondansetron, or other dietary interventions are effective in treating hyperemesis gravidarum.
Corticosteroids may be more effective than metoclopramide at reducing vomiting episodes and reducing readmission to the intensive care unit in women with hyperemesis gravidarum.
PMCID: PMC2907767  PMID: 21726485
11.  Aripiprazole in the Maintenance Treatment of Bipolar Disorder: A Critical Review of the Evidence and Its Dissemination into the Scientific Literature 
PLoS Medicine  2011;8(5):e1000434.
A systematic search of the literature reveals limited evidence to support use of aripiprazole, a second-generation antipsychotic medication, in maintenance therapy of bipolar disorder, despite widespread use.
Background
Aripiprazole, a second-generation antipsychotic medication, has been increasingly used in the maintenance treatment of bipolar disorder and received approval from the U.S. Food and Drug Administration for this indication in 2005. Given its widespread use, we sought to critically review the evidence supporting the use of aripiprazole in the maintenance treatment of bipolar disorder and examine how that evidence has been disseminated in the scientific literature.
Methods and Findings
We systematically searched multiple databases to identify double-blind, randomized controlled trials of aripiprazole for the maintenance treatment of bipolar disorder while excluding other types of studies, such as open-label, acute, and adjunctive studies. We then used a citation search to identify articles that cited these trials and rated the quality of their citations. Our evidence search protocol identified only two publications, both describing the results of a single trial conducted by Keck et al., which met criteria for inclusion in this review. We describe four issues that limit the interpretation of that trial as supporting the use of aripiprazole for bipolar maintenance: (1) insufficient duration to demonstrate maintenance efficacy; (2) limited generalizability due to its enriched sample; (3) possible conflation of iatrogenic adverse effects of abrupt medication discontinuation with beneficial effects of treatment; and (4) a low overall completion rate. Our citation search protocol yielded 80 publications that cited the Keck et al. trial in discussing the use of aripiprazole for bipolar maintenance. Of these, only 24 (30%) mentioned adverse events reported and four (5%) mentioned study limitations.
Conclusions
A single trial by Keck et al. represents the entirety of the literature on the use of aripiprazole for the maintenance treatment of bipolar disorder. Although careful review identifies four critical limitations to the trial's interpretation and overall utility, the trial has been uncritically cited in the subsequent scientific literature.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Bipolar disorder (manic depression) is a serious, long-term mental illness that affects about 1% of adults at some time during their life. It usually develops in late adolescence or early adulthood and affects men and women from all backgrounds. People with bipolar disorder experience wild mood swings that interfere with daily life and damage relationships. During “manic” episodes, which can last several months if untreated, they may feel euphoric (“high”), energetic, or irritable. They may be full of ambitious plans, feel creative, and spend money recklessly. They can also have psychotic symptoms—they may see or hear things that are not there. During depressive episodes, affected individuals may feel helpless, worthless, and suicidal. Treatments for bipolar disorder include drugs to stabilize mood swings (for example, lithium and anticonvulsant medications), antidepressants to treat depressive episodes, and antipsychotic drugs to treat manic episodes. Psychotherapy can also help and patients can be taught to recognize the signs of approaching manic or depressive episodes and the triggers for these episodes.
Why Was This Study Done?
Treatment of bipolar disorder is divided into three phases: acute treatment lasting about 2 months to achieve remission, continuance treatment lasting from months 2 through 6 to prevent relapse, and long-term maintenance treatment to prevent recurrence. Second-generation (atypical) antipsychotics are widely used for acute treatment of manic episodes but are also used for maintenance treatment. For example, the atypical antipsychotic aripiprazole, which gained US approval for this indication in 2005, is now a popular choice among clinicians for treating bipolar disorder. But how much evidence is there to support aripiprazole's use in the maintenance treatment of bipolar disorder? Here, the researchers systematically search the published literature for double-blind randomized controlled trials of aripiprazole for this indication, critically analyze the quality of these trials, and undertake a citation search to investigate how the results of these trials have been disseminated in the scientific literature. In double-blind randomized controlled trials, patients are randomly assigned to receive a test drug or a control (generally, placebo), and the effects of these drugs compared; patients in the trial, and physicians administering treatments, would not know who is receiving the test drug or control until the trial is completed.
What Did the Researchers Do and Find?
The researchers' search for reports of double-blind randomized controlled trials of aripiprazole for the maintenance treatment of bipolar disorder using predefined criteria identified only two publications, both describing a single trial—the Keck trial. Critical review of this trial identified four issues that limit its interpretation for supporting aripiprazole as a maintenance therapy: the trial was too short to demonstrate maintenance efficacy; all the trial participants had responded well to aripiprazole as an acute treatment so the generalizability of the trial's results was limited; the trial design meant that some of the apparent beneficial treatment results could have reflected the adverse effects of abrupt medication discontinuation in the control group; and the trial had a low completion rate. The researchers' citation search identified 80 publications that cited the Keck trial in discussions of the use of aripiprazole for maintenance treatment of bipolar disorder. Only a quarter of these papers presented any numerical data from the trial, only a third mentioned any of the reported adverse events, and only four papers mentioned the trial's limitations.
What Do These Findings Mean?
This evaluation of the evidence base supporting the use of aripiprazole for the maintenance treatment of bipolar disorder shows that the justification for this practice relies on the results of one published trial. Moreover, the methodology and reporting of this trial mean that its results cannot easily be generalized to inform the treatment of most patients with bipolar disorder. Worryingly, the researchers' citation search indicates that the Keck trial has been cited uncritically in the ensuing scientific literature. Although the unique features of bipolar disorder make it hard to undertake controlled studies of treatment options, the researchers express concern that “the publication and apparently uncritical acceptance of this trial may be diverting patients away from more effective treatments”.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000434.
The US National Institute of Mental Health has detailed information on bipolar disorder, including an Easy to Read booklet (in English and Spanish)
The UK National Health Service Choices website provides information on all aspects of bipolar disorder
The UK charity Mind has information on bipolar disorder and provides links to other useful organizations
MedlinePlus has links to further information on bipolar disorder (in English and Spanish)
doi:10.1371/journal.pmed.1000434
PMCID: PMC3086871  PMID: 21559324
12.  Oral Ondansetron Administration in Emergency Departments to Children with Gastroenteritis: An Economic Analysis 
PLoS Medicine  2010;7(10):e1000350.
Stephen Freedman and colleagues performed a cost analysis of the routine administration of ondansetron in both the United States and Canada and show that its routine administration to eligible children in such settings could provide substantial benefit.
Background
The use of antiemetics for children with vomiting is one of the most controversial decisions in the treatment of gastroenteritis in developed countries. Ondansetron, a selective serotonin receptor antagonist, has been found to be effective in improving the success of oral rehydration therapy. However, North American and European clinical practice guidelines continue to recommend against its use, stating that evidence of cost savings would be required to support ondansetron administration. Thus, an economic analysis of the emergency department administration of ondansetron was conducted. The primary objective was to conduct a cost analysis of the routine administration of ondansetron in both the United States and Canada.
Methods and Findings
A cost analysis evaluated oral ondansetron administration to children presenting to emergency departments with vomiting and dehydration secondary to gastroenteritis from a societal and health care payer's perspective in both the US and Canada. A decision tree was developed that incorporated the frequency of vomiting, intravenous insertion, hospitalization, and emergency department revisits. Estimates of the monetary costs associated with ondansetron use, intravenous rehydration, and hospitalization were derived from administrative databases or emergency department use. The economic burden in children administered ondansetron plus oral rehydration therapy was compared to those not administered ondansetron employing deterministic and probabilistic simulations. We estimated the costs or savings to society and health care payers associated with the routine administration of ondansetron. Sensitivity analyses considered variations in costs, treatment effects, and exchange rates. In the US the administration of ondansetron to eligible children would prevent approximately 29,246 intravenous insertions and 7,220 hospitalizations annually. At the current average wholesale price, its routine administration to eligible children would annually save society US$65.6 million (US$49.1–US$81.1) and health care payers US$61.1 million (US$46.2–US$76.3). In Canada the administration of ondansetron to eligible children would prevent 4,065 intravenous insertions and 1,003 hospitalizations annually. Its routine administration would annually save society CDN$1.72 million (CDN$1.15–CDN$1.89) and the health care system CDN$1.18 million (CDN$0.88–CDN$1.41).
Conclusions
In countries where intravenous rehydration is often employed, the emergency department administration of oral ondansetron to children with dehydration and vomiting secondary to gastroenteritis results in significant monetary savings compared to a no-ondansetron policy.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Although many episodes of gastroenteritis in children are mild and can be managed with oral fluids, including oral rehydration therapy (ORT), some cases are severe enough to require hospital admission for intravenous fluids. Administration of an antiemetic (a drug that reduces nausea and sickness) can be clinically effective, especially ondansetron, (a drug that belongs to a class of drugs known as selective serotonin receptor antagonists), which is safer than other antiemetics, such as promethazine and prochlorperazine, and in which there is good evidence to support its effectiveness in improving the success of ORT in children with gastroenteritis. Furthermore, studies have shown that administration of ondansetron decreases the risk of further vomiting, and hence the need for intravenous rehydration, and immediate hospital admission. However, despite the proven clinical benefits of ondansetron, clinical practice guidelines continue to recommend against the use of antiemetics in gastroenteritis because the evidence of cost savings is not yet clear. Last year, the UK's National Institute for Health and Clinical Excellence recommended that such a cost analysis should be a key research priority in pediatric gastroenteritis.
Why Was This Study Done?
This study—which is an economic analysis—was conducted in response to the various calls for the need to demonstrate the cost effectiveness of ondansetron in the management of pediatric gastroenteritis.
What Did the Researchers Do and Find?
The researchers analysed the costs of the administration of oral ondansetron in both the US and Canada, if routinely given to children with gastroenteritis-induced vomiting and dehydration in the emergency department setting. In addition, the researchers calculated the incremental cost of ondansetron per quality-adjusted life-year (QALY) gained from a health care perspective, compared to a regimen without ondansetron administration. The authors conducted a particular type of statistical analysis, known as decision tree analysis, to compare the two treatment options—administering ondansetron and not administering ondansetron in addition to ORT, with the clinical outcomes (further vomiting, intravenous rehydration, and hospitalization) determined on the basis of the documented efficacy of ondansetron. In addition, the researchers conducted their analyses from both the societal perspective (which included all costs, both direct—the resources required to produce a service; and indirect—productivity costs) and the health care payer's perspective. The US and Canada use similar medical resources, management programs, and treatment guidelines, but as prices differ dramatically (for example, the cost of hospitalization in the US is 8-fold higher than that in Canada), the researchers conducted a separate analysis for each country.
On the basis of data from the US, the researchers found that the administration of ondansetron to eligible children would prevent approximately 29,246 intravenous insertions and 7,220 hospitalizations every year with an annual saving of US$65.6 million to society and US$61.1 million to payers of health care costs if this drug was given routinely. When using Canadian data, the researchers found that the administration of ondansetron to eligible children would prevent 4,065 intravenous insertions and 1,003 hospitalizations every year, with an annual saving of CDN$1.72 million to society and CDN$1.18 million to payers of health care costs if this drug was given routinely.
What Do These Findings Mean?
The results of this study show that the emergency department administration of oral ondansetron to children with dehydration and vomiting secondary to gastroenteritis results in significant monetary savings from both societal and health care perspectives compared to a policy that does not include ondansetron administration. Furthermore, the societal savings are probably an underestimate because in their model, the researchers assumed that only 10% of children with gastroenteritis presenting to an emergency department would meet eligibility criteria (in reality, this proportion would likely be higher). In addition, the researchers did not include estimates for ondansetron administration in the clinic or private office setting, as although such use is common, no estimates of eligibility and efficacy were available.
Therefore, in addition to being clinically beneficial, the administration of oral ondansetron to children with dehydration and vomiting secondary to gastroenteritis is also economically advantageous.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000350.
Patient UK and the US National Institutes of Health provide information for patients on ondansetron
Patient UK provides information on gastroenteritis in children
BBC Health also provides general information on gastroenteritis
The Centers for Disease Control and Prevention contains a report on managing acute gastroenteritis among children
doi:10.1371/journal.pmed.1000350
PMCID: PMC2953527  PMID: 20967234
13.  Nausea and vomiting in people with cancer and other chronic diseases 
Clinical Evidence  2009;2009:2406.
Introduction
Nausea and vomiting occur in 40%–70% of people with cancer, and are also common in other chronic conditions such as hepatitis C and inflammatory bowel disease. Nausea and vomiting become more common as disease progresses.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for nausea and vomiting occurring as a result of either the disease or its treatment in adults with cancer? What are the effects of treatments for nausea and vomiting occurring as a result of either the disease or its treatment in adults with chronic diseases other than cancer? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found nine systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: 5HT3 antagonists, antihistamines, antimuscarinics, atypical antipsychotics, benzodiazepines, butyrophenones, cannabinoids, corticosteroids, haloperidol, metoclopramide, NK1 antagonists, phenothiazines, prokinetics, 5HT3 antagonists plus corticosteroids, and venting gastrostomy.
Key Points
Nausea and vomiting occur in 40%–70% of people with cancer, and are also common in other chronic conditions such as hepatitis C and inflammatory bowel disease. Nausea and vomiting become more common as disease progresses.
Nausea and vomiting may occur as a result of the disease or its treatment.
The evidence base for treatment-related causes of nausea and vomiting (chemotherapy and radiotherapy) is much greater and more robust than for disease-related causes.
Metoclopramide is likely to be effective for reducing episodes of vomiting in people having chemotherapy. Dexamethasone, in combination with other antiemetics, reduces acute and delayed emesis compared with placebo in people receiving emetogenic chemotherapy, and it may be more effective than metoclopramide in this population. 5HT3 antagonists also reduce acute vomiting in people having chemotherapy compared with metoclopramide-based regimens, and this benefit is enhanced by the addition of dexamethasone.There is consensus that haloperidol, phenothiazines, and venting gastrostomy are effective for controlling nausea and vomiting in people with cancer.
Cannabinoids are effective for nausea and vomiting in people receiving chemotherapy, but may be associated with a high and often unacceptable burden of adverse effects.
We don't know whether antihistamines, antimuscarinics, antipsychotics, benzodiazepines, or NK1 antagonists are effective in people with cancer-related nausea and vomiting.
We don't know whether 5HT3 antagonists alone reduce nausea and vomiting in people having radiotherapy. However, adding dexamethasone to 5HT3 antagonists seems more effective than 5HT3 antagonists alone.
Despite the lack of robust RCT evidence, there is a consensus based on clinical experience that antihistamines have a place in the management of nausea and vomiting, especially that related to motion sickness, mechanical bowel obstruction, and raised intracranial pressure. We don't know whether any other interventions are effective for controlling nausea and vomiting in people with chronic conditions other than cancer.
PMCID: PMC2907825  PMID: 19445763
14.  Gastric volvulus 
Emergency Medicine Journal : EMJ  2007;24(6):446-447.
Gastric volvulus is a rare disease with an unknown incidence. Unless it stays in the back of the diagnostician's mind, diagnosis of gastric volvulus, which can have significant morbidity and mortality associated with it, can be easily missed. Unstable vital signs and distressed appearance are not always present, as in textbook cases. The presence of a hiatal hernia with persistent vomiting despite initial antiemetic treatment should trigger one to think of gastric volvulus, despite the patient appearing very stable. With the advent of CT and laparoscopic surgery, the gold standards for diagnosing and treating this disease are ever evolving.
doi:10.1136/emj.2006.041947
PMCID: PMC2658296  PMID: 17513555
15.  A Rare but Serious Complication of Ladd's Procedure: Recurrent Midgut Volvulus 
Case Reports in Gastroenterology  2007;1(1):130-134.
An eighteen-month-old boy who had undergone a Ladd's procedure for malrotation in the newborn period presented with acute onset of nausea, vomiting, rectal bleeding, and confusion. Laparotomy revealed midgut volvulus, mesenteric lymphadenopathy and massive chylous ascites. Recurrent midgut volvulus following Ladd's procedure is extremely rare but should be borne in mind in cases of persistent or recurrent gastrointestinal symptoms. Timely surgery is necessary to avoid intestinal gangrene and decrease morbidity and mortality related to consequences of midgut volvulus.
doi:10.1159/000110601
PMCID: PMC3073800  PMID: 21487558
Intestinal malrotation; Midgut volvulus, recurrent
16.  Pediatric gastric volvulus--experience with 7 cases. 
Gastric volvulus, organoaxial or mesenterioaxial, is a rare condition in infancy and childhood. We experienced 7 cases of pediatric gastric volvulus, consisting of 3 cases of secondary gastric volvulus due to left diaphragmatic eventration or paraesophageal hernia and 4 cases of idiopathic gastric volvulus. Of 7 cases, five were organoaxial in type and two were mesenterioaxial. The main symptoms of secondary gastric volvulus were vomiting and respiratory difficulty whereas those of idiopathic gastric volvulus were abdominal distension and weight loss with or without failure to thrive. It may be suspected on plain abdominal radiographs and usually confirmed by upper gastrointestinal series. Upper gastrointestinal series in organaxial volvulus demonstrated characteristic findings such as reversal of the greater and lesser curvatures and two air-fluid levels. In mesenterioaxial volvulus, the stomach was rotated into inverted position with pyloroantral obstruction showing a beak appearance. The three patients with secondary volvulus underwent repair of associated defect with or without gastropexy and the 3 patients with idiopathic volvulus underwent anterior gastropexy or gastrostomy. In those with idiopathic gastric volvulus, there was no obvious cause such as laxity of the perigastric ligaments. The operative results were satisfactory except for the three patients with idiopathic gastric volvulus whose abdomen remained distended regardless of weight gain.
PMCID: PMC3053782  PMID: 1285925
17.  Giant mesenteric lymphatic malformation presenting as small bowel volvulus 
Journal of Surgical Case Reports  2013;2013(9):rjt083.
Abdominal pain with bilious emesis is an ominous clinical presentation with many possible causes. We describe a previously healthy 4-year-old boy who presented with these symptoms and ultrasound findings of fluid throughout most of the abdominal cavity. Computed tomography imaging revealed a large cystic mass (21-by-13 cm) associated with a small bowel obstruction due to volvulus. A laparoscopic exploration was undertaken, revealing a large mass arising from the small intestinal mesentery and causing a segmental volvulus of the small bowel. Conversion to mini-laparotomy allowed reduction of the volvulus and segmental resection of the small bowel associated with a giant mesenteric lymphatic malformation. This case describes a rare cause of intestinal volvulus due to a mesenteric lymphatic malformation.
doi:10.1093/jscr/rjt083
PMCID: PMC3813682  PMID: 24963906
18.  Consciousness, Cognition and the Cognitive Apparatus in the Vedānta Tradition 
Mens Sana Monographs  2011;9(1):54-78.
A human being is a complex entity consisting of the Self (also known as Consciousness), mind, senses and the body. The Vedānta tradition holds that the mind, the senses and the body are essentially different from the Self or Consciousness. It is through consciousness that we are able to know the things of the world, making use of the medium of the mind and the senses. Furthermore, the mind, though material, is able to reveal things, borrowing the light from consciousness. From the phenomenological point of view, we have to answer the following questions: how does one know the mind/the mental operations/the cogitations of the mind? Does the mind know itself? Is it possible? There is, again, the problem of the intentionality of consciousness. Is consciousness intentional? According to Vedānta, consciousness by its very nature is not intentional, but it becomes intentional through the mind. The mind or the ego is not part of the consciousness; on the contrary, it is transcendent to consciousness. It is difficult to spell out the relation between consciousness and the mind. How does consciousness, which is totally different from the mind, get related to the mind in such a way that it makes the latter capable of comprehending the things of the world? The Vedānta tradition provides the answer to this question in terms of the knower-known relation. Consciousness is pure light, self-luminous by its very nature, that is, although it reveals other objects, it is not revealed by anything else. When Sartre describes it as nothingness, bereft of even ego, it is to show that it is pure light revealing objects outside it.
doi:10.4103/0973-1229.77427
PMCID: PMC3115303  PMID: 21694962
Consciousness; Self; Vedānta tradition; Mind; Self; Intentionality; Sartre; Śankara; Popper; Husserl; Enworlded subjectivity
19.  Metastatic breast cancer presenting as a gallstone ileus 
Journal of Surgical Case Reports  2013;2013(12):rjt113.
Metastatic breast cancer to the small bowel (SB) presenting as gallstone ileus and resulting in SB obstruction has not been described previously. A 76-year-old woman with previous metastatic breast cancer to the axial spine and hips presented with abdominal pain and bilious vomiting. CT scanning revealed SB obstruction consistent with gallstone ileus. The patient underwent two segmental SB resections for distal ileal strictures mimicking what appeared to be macroscopic Crohn's disease. The entero-biliary fistula was undisturbed. Pathological analysis revealed the dual pathologies of gallstone ileus and metastatic carcinoma from a breast primary causing luminal SB obstruction. Improvements in staging and treatment modalities have contributed to the increased overall long-term survival for breast cancer, compelling clinicians to consider metastatic breast cancer as a differential diagnosis in women presenting with new onset of gastrointestinal symptoms in order that appropriate treatment be administered in a timely fashion.
doi:10.1093/jscr/rjt113
PMCID: PMC3888007  PMID: 24968443
20.  Renal amyloidosis in Whipple disease: a case report 
Cases Journal  2009;2:8444.
Introduction
Whipple disease is a rare systemic infection caused by Tropheryma whippelii that usually manifests with joint pain, weight loss, diarrhoea and abdominal pain. However, in some cases the infection may involve other organs and tissues.
Case presentation
We report on a 44-year-old man with Whipple disease which led to renal amyloidosis and end-stage renal failure. In this case, the patient was diagnosed with Whipple disease and commenced on a 12-month trimetoprime-sulfametoxasole therapy with good result. Six months after cessation of therapy the patient was readmitted to hospital due to signs of renal failure. An urgent kidney biopsy was performed which revealed secondary amyloidosis. Despite intensive immunosuppressive treatment, renal parameters gradually deteriorated and haemodialysis was started eventually. Three months later the patient’s general condition dramatically worsened with bloody diarrhoea, bilious vomiting and progressive malnutrition. The repeated endoscopic examination confirmed severe recurrence of Whipple disease. Ceftriaxone and total parenteral nutrition was started what greatly improved patient’s state.
Conclusions
To our knowledge based on systematic review, this is the first case report on Whipple disease complicated by secondary amyloidosis and kidney failure maintained on permanent renal replacement therapy. It is strongly suspected that the use of immunosuppressive treatment in such cases may exacerbate the course of Whipple disease and cause life-threatening complications.
doi:10.4076/1757-1626-2-8444
PMCID: PMC2769443  PMID: 19918433
21.  Improvement in Survival after Paraquat Ingestion Following Introduction of a New Formulation in Sri Lanka 
PLoS Medicine  2008;5(2):e49.
Background
Pesticide ingestion is a common method of self-harm in the rural developing world. In an attempt to reduce the high case fatality seen with the herbicide paraquat, a novel formulation (INTEON) has been developed containing an increased emetic concentration, a purgative, and an alginate that forms a gel under the acid conditions of the stomach, potentially slowing the absorption of paraquat and giving the emetic more time to be effective. We compared the outcome of paraquat self-poisoning with the standard formulation against the new INTEON formulation following its introduction into Sri Lanka.
Methods and Findings
Clinical data were prospectively collected on 586 patients with paraquat ingestion presenting to nine large hospitals across Sri Lanka with survival to 3 mo as the primary outcome. The identity of the formulation ingested after October 2004 was confirmed by assay of blood or urine samples for a marker compound present in INTEON. The proportion of known survivors increased from 76/297 with the standard formulation to 103/289 with INTEON ingestion, and estimated 3-mo survival improved from 27.1% to 36.7% (difference 9.5%; 95% confidence interval [CI] 2.0%–17.1%; p = 0.002, log rank test). Cox proportional hazards regression analyses showed an approximately 2-fold reduction in toxicity for INTEON compared to standard formulation. A higher proportion of patients ingesting INTEON vomited within 15 min (38% with the original formulation to 55% with INTEON, p < 0.001). Median survival time increased from 2.3 d (95% CI 1.2–3.4 d) with the standard formulation to 6.9 d (95% CI 3.3–10.7 d) with INTEON ingestion (p = 0.002, log rank test); however, in patients who did not survive there was a comparatively smaller increase in median time to death from 0.9 d (interquartile range [IQR] 0.5–3.4) to 1.5 d (IQR 0.5–5.5); p = 0.02.
Conclusions
The survey has shown that INTEON technology significantly reduces the mortality of patients following paraquat ingestion and increases survival time, most likely by reducing absorption.
Martin Wilks and colleagues compared the outcome of paraquat self-poisoning with the standard formulation against a new formulation following its introduction into Sri Lanka.
Editors' Summary
Background.
Paraquat is a non-selective herbicide used in many countries on a variety of crops including potatoes, rice, maize, tea, cotton, and bananas. It is fast-acting, rainfast, and facilitates “no-till” farming, but it has attracted controversy because of the potential for misuse, particularly in developing countries. Better training of workers has been shown to reduce the number of accidents, and additions to the liquid formulation have contributed to a reduction in cases where paraquat was drunk by mistake—blue color and a stench agent made it less attractive to drink, and an emetic to induce vomiting aimed to reduce the time it is retained in the body.
Why Was This Study Done?
Despite the changes made to the formulation, paraquat is still taken deliberately as a poison by agricultural workers in parts of the developing world. Although other pesticides cause more deaths overall, paraquat poisoning is more frequently fatal than other common pesticides. Syngenta, a commercial producer of paraquat, has developed a new paraquat formulation designed to reduce its toxicity. Syngenta introduced the new formulation in Sri Lanka, a country well known for its high level of suicides with pesticides, in 2004. This new formulation includes three components designed to reduce paraquat absorption from the stomach and intestines: a gelling agent to thicken the formulation in the acidic environment of the stomach and slow its passage into the small intestine; an increase in the amount of emetic to induce more vomiting more quickly; and a purgative to speed its exit from the small intestine, the main site of its absorption. The researchers wished to know whether the new formulation could contribute to improved survival in instances where paraquat had been ingested.
What Did the Researchers Do and Find?
The researchers gathered information on the time and circumstances of when paraquat was taken, the amount that was taken, the times, and details of any vomiting, treatment, and outcomes for cases of attempted suicide by paraquat poisoning at nine large hospitals in agricultural regions of Sri Lanka from December 2003 to January 2006. In total, 774 patients were tracked in this time. Syngenta introduced the new formulation in Sri Lanka on 1 October 2004. The researchers gathered information on the formulation involved in subsequent cases, by either interview or analysis of samples. After excluding some unusual or less certain cases, they analyzed data on 586 patients, of whom 297 had deliberately taken the standard formulation and 289 the new formulation.
Although the new formulation was still toxic, the data showed an increase in the proportion of cases surviving for at least three months—from 27% (standard formulation) to 37% (new formulation), an effect that was unlikely to be due to chance. More patients vomited within 15 minutes of taking the new formulation of paraquat. Patients who died generally survived longer if they had taken the new rather than the standard formulation. The researchers estimated that the new formulation is just over half as toxic as the standard formulation, meaning that a patient was likely to suffer the same level of ill effects after taking twice as much of the new formulation compared to the standard formulation.
What Do these Findings Mean?
This study was designed, funded, and led by Syngenta, the manufacturer of the standard and new formulations of paraquat but the study team included a number of independent Sri Lankan and international scientists. As the researchers observed the effects of the introduction of the new formulation across the entire country at the same time, they could not completely rule out other possible reasons for the differences in outcomes for those who had taken the two formulations, such as differences in treatment.
Despite this inherent drawback, the researchers estimate that during the study the new formulation saved about 30 lives. They conclude that the the new formulation does reduce the amount of paraquat absorbed by the body, although the study does not answer the question whether this was due to the gelling agent, the increased emetic in the new formulation or a combination of factors. The researchers suggest that the new formulation, by keeping patients alive longer, may allow doctors more time to treat patients. As no effective treatment exists at present, this benefit relies on a treatment being developed in the future.
The researchers note that the most important factor in predicting the outcome when paraquat has been taken deliberately is the dose. As a result, they suggest that the new formulation can only be one part of a wider strategy to reduce deaths by deliberate self-poisoning using paraquat. They suggest that such an integrated approach might include generic measures to reduce incidents of self-harm, reduced access to paraquat, reduced formulation strength, and improvements in treatment.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050049.
The US Environmental Protection Agency has published its Reregistration Eligibility Decision for paraquat
The Department of Health and Human Services of the US Centers for Disease Control and Prevention provides a fact sheet on how to handle paraquat and suspected cases of exposure
The World Health Organisation has recently finished consulting on a draft Poisons Information Monograph for paraquat
The International Programme on Chemical Safety (IPCS) has published a review of paraquat in its Environmental Health Criteria Series
MedlinePlus provides links to information on health effects of paraquat
doi:10.1371/journal.pmed.0050049
PMCID: PMC2253611  PMID: 18303942
22.  Chimpanzees do not take into account what others can hear in a competitive situation 
Animal Cognition  2007;11(1):175-178.
Chimpanzees (Pan troglodytes) know what others can and cannot see in a competitive situation. Does this reflect a general understanding the perceptions of others? In a study by Hare et al. (2000) pairs of chimpanzees competed over two pieces of food. Subordinate individuals preferred to approach food that was behind a barrier that the dominant could not see, suggesting that chimpanzees can take the visual perspective of others. We extended this paradigm to the auditory modality to investigate whether chimpanzees are sensitive to whether a competitor can hear food rewards being hidden. Results suggested that the chimpanzees did not take what the competitor had heard into account, despite being able to locate the hiding place themselves by the noise.
doi:10.1007/s10071-007-0097-0
PMCID: PMC2757587  PMID: 17558526
Social cognition; Food competition; Perspective taking
23.  Intestinal Malrotation and Catastrophic Volvulus in Infancy 
The Journal of Emergency Medicine  2012;43(1):e49-e51.
Background
Intestinal malrotation in the newborn is usually diagnosed after signs of intestinal obstruction, such as bilious emesis, and corrected with the Ladd procedure.
Objectives
The objective of this report is to describe the presentation of severe cases of midgut volvulus presenting in infancy, and to discuss the characteristics of these cases.
Case Report
We performed a seven year review at our institution and present two cases of catastrophic midgut volvulus presenting in the post-neonatal period, ending in death soon after the onset of symptoms. These two patients also had significant laboratory abnormalities compared to patients with more typical presentations resulting in favorable outcomes.
Conclusions
While most cases of intestinal malrotation in infancy can be treated successfully, in some circumstances, patients’ symptoms may not be detected early enough for effective treatment, and therefore may result in catastrophic midgut volvulus and death.
doi:10.1016/j.jemermed.2011.06.135
PMCID: PMC3351570  PMID: 22325550
Malrotation; midgut volvulus; neonatal intensive care
24.  Obligatory symbiotic Wolbachia endobacteria are absent from Loa loa 
Filaria Journal  2003;2:10.
Background
Many filarial nematodes harbour Wolbachia endobacteria. These endobacteria are transmitted vertically from one generation to the next. In several filarial species that have been studied to date they are obligatory symbionts of their hosts. Elimination of the endobacteria by antibiotics interrupts the embryogenesis and hence the production of microfilariae. The medical implication of this being that the use of doxycycline for the treatment of human onchocerciasis and bancroftian filariasis leads to elimination of the Wolbachia and hence sterilisation of the female worms. Wolbachia play a role in the immunopathology of patients and may contribute to side effects seen after antifilarial chemotherapy. In several studies Wolbachia were not observed in Loa loa. Since these results have been doubted, and because of the medical significance, several independent methods were applied to search for Wolbachia in L. loa.
Methods
Loa loa and Onchocerca volvulus were studied by electron microscopy, histology with silver staining, and immunohistology using antibodies against WSP, Wolbachia aspartate aminotransferase, and heat shock protein 60. The results achieved with L. loa and O. volvulus were compared. Searching for Wolbachia, genes were amplified by PCR coding for the bacterial 16S rDNA, the FTSZ cell division protein, and WSP.
Results
No Wolbachia endobacteria were discovered by immunohistology in 13 male and 14 female L. loa worms and in numerous L. loa microfilariae. In contrast, endobacteria were found in large numbers in O. volvulus and 14 other filaria species. No intracellular bacteria were seen in electron micrographs of oocytes and young morulae of L. loa in contrast to O. volvulus. In agreement with these results, Wolbachia DNA was not detected by PCR in three male and six female L. loa worms and in two microfilariae samples of L. loa.
Conclusions
Loa loa do not harbour obligatory symbiotic Wolbachia endobacteria in essential numbers to enable their efficient vertical transmission or to play a role in production of microfilariae. Exclusively, the filariae cause the immunopathology of loiasis is patients and the adverse side effects after antifilarial chemotherapy. Doxycycline cannot be used to cure loiais but it probably does not represent a risk for L. loa patients when administered to patients with co-infections of onchocerciasis.
doi:10.1186/1475-2883-2-10
PMCID: PMC161789  PMID: 12801420
25.  Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Negative Women: A Multicentre Randomized Controlled Trial 
PLoS Medicine  2014;11(9):e1001733.
Clara Menéndez and colleagues conducted an open-label randomized controlled trial in HIV-negative pregnant women in Benin, Gabon, Mozambique, and Tanzania to evaluate the safety and efficacy of mefloquine compared to sulfadoxine-pyrimethamine for intermittent preventative therapy for malaria.
Please see later in the article for the Editors' Summary
Background
Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by WHO to prevent malaria in African pregnant women. The spread of SP parasite resistance has raised concerns regarding long-term use for IPT. Mefloquine (MQ) is the most promising of available alternatives to SP based on safety profile, long half-life, and high efficacy in Africa. We evaluated the safety and efficacy of MQ for IPTp compared to those of SP in HIV-negative women.
Methods and Findings
A total of 4,749 pregnant women were enrolled in an open-label randomized clinical trial conducted in Benin, Gabon, Mozambique, and Tanzania comparing two-dose MQ or SP for IPTp and MQ tolerability of two different regimens. The study arms were: (1) SP, (2) single dose MQ (15 mg/kg), and (3) split-dose MQ in the context of long lasting insecticide treated nets. There was no difference on low birth weight prevalence (primary study outcome) between groups (360/2,778 [13.0%]) for MQ group and 177/1,398 (12.7%) for SP group; risk ratio [RR], 1.02 (95% CI 0.86–1.22; p = 0.80 in the ITT analysis). Women receiving MQ had reduced risks of parasitemia (63/1,372 [4.6%] in the SP group and 88/2,737 [3.2%] in the MQ group; RR, 0.70 [95% CI 0.51–0.96]; p = 0.03) and anemia at delivery (609/1,380 [44.1%] in the SP group and 1,110/2743 [40.5%] in the MQ group; RR, 0.92 [95% CI 0.85–0.99]; p = 0.03), and reduced incidence of clinical malaria (96/551.8 malaria episodes person/year [PYAR] in the SP group and 130/1,103.2 episodes PYAR in the MQ group; RR, 0.67 [95% CI 0.52–0.88]; p = 0.004) and all-cause outpatient attendances during pregnancy (850/557.8 outpatients visits PYAR in the SP group and 1,480/1,110.1 visits PYAR in the MQ group; RR, 0.86 [0.78–0.95]; p = 0.003). There were no differences in the prevalence of placental infection and adverse pregnancy outcomes between groups. Tolerability was poorer in the two MQ groups compared to SP. The most frequently reported related adverse events were dizziness (ranging from 33.9% to 35.5% after dose 1; and 16.0% to 20.8% after dose 2) and vomiting (30.2% to 31.7%, after dose 1 and 15.3% to 17.4% after dose 2) with similar proportions in the full and split MQ arms. The open-label design is a limitation of the study that affects mainly the safety assessment.
Conclusions
Women taking MQ IPTp (15 mg/kg) in the context of long lasting insecticide treated nets had similar prevalence rates of low birth weight as those taking SP IPTp. MQ recipients had less clinical malaria than SP recipients, and the pregnancy outcomes and safety profile were similar. MQ had poorer tolerability even when splitting the dose over two days. These results do not support a change in the current IPTp policy.
Trial registration
ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001429343
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Half the world's population is at risk of malaria, a mosquito-borne parasitic disease that kills about 600,000 people every year. Most of these deaths occur among young children in sub-Saharan Africa but pregnant women and their unborn children living in Africa are also very vulnerable to malaria. Infection with malaria during pregnancy can cause severe maternal anemia (reduced red blood cell numbers), stillbirths, and pre-term and low-birthweight babies, and is responsible for the deaths of many African babies and women. To prevent this loss of life, the World Health Organization (WHO) recommends a three-pronged approach—the delivery to pregnant women of the antimalarial drug sulfadoxine-pyrimethamine (SP) at each scheduled antenatal care visit given at least one month apart (intermittent preventive treatment in pregnancy; IPTp), the use of insecticide treated bed nets to protect pregnant women from the bites of infected mosquitoes, and effective case management of pregnant women with malarial illness.
Why Was This Study Done?
IPTp with SP reduces the delivery of low-birth-weight babies and neonatal deaths but malaria parasites are becoming resistant to SP. Thus, other antimalarial drugs need to be evaluated for use in IPTp. Suitable drugs need to remain in the body for a long time to maximize their prophylactic (preventative) effect, they need to be given as a single dose at antenatal clinic visits to ensure compliance, and they must not harm the unborn child. In this open-label, randomized controlled trial (RCT), the researchers compare the efficacy and safety of IPTp with SP and mefloquine (MQ, an antimalarial drug that matches these criteria) in HIV-negative women living in Africa. The study also compares the tolerability of two MQ regimens. RCTs compare outcomes in groups of people chosen to receive different interventions through the play of chance; in open-label RCTs, both the researchers and the study participants know which treatment is being administered. IPTp with SP is only recommended for HIV-negative women because SP interacts with cotrimoxazole, which is routinely given to HIV-positive individuals to prevent infections.
What Did the Researchers Do and Find?
The researchers assigned 4,749 pregnant women in Benin, Gabon, Mozambique, and Tanzania to one of three study groups. Participants in the SP and MQ groups received two doses of SP or MQ, respectively, administered at least one month apart. Participants in the split-dose MQ group received each MQ dose as half doses given on consecutive days. The prevalence of low-birth-weight deliveries (the study's primary outcome; the prevalence of a condition is the proportion of a population with that condition) was similar in the SP group and in the combined MQ groups. However, compared to women who received SP, women who received MQ had a lower risk of parasitemia (parasites in the blood), a lower risk of anemia at delivery, fewer episodes of clinical malaria, and fewer outpatient attendances. The prevalence of placental infection with malaria parasites and of adverse pregnancy outcomes such as stillbirth was similar in all the study groups. Finally, the tolerability of IPTp was poorer in the two MQ intervention groups than in the SP group, but similar proportions of adverse events (mainly dizziness and vomiting) were reported for the two MQ dosing regimens.
What Do These Findings Mean?
These findings indicate that HIV-negative African women taking MQ for IPTp had a similar risk of a low-birth-weight delivery (the study's primary outcome) and lower risk of malaria illness during pregnancy than women taking SP for IPTp. Because the study did not have a no-IPTp arm (for ethical reasons), these findings provide no information about the efficacy or safety or either MQ or SP per se; these findings only indicate that MQ is no more efficacious than SP in the prevention of low-birth-weight babies. Moreover, because the study was open-label, the accuracy of the findings related to the tolerability and safety of MQ compared to SP may be limited because of biases in the assessment of safety outcomes. Given that the MQ dose used here for IPTp was associated with poorer tolerability than that of SP, these findings do not support the use of MQ instead of SP for IPTp.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001733.
A related PLOS Medicine Research Article by Raquel González and colleagues examines IPTp-MQ in HIV-infected women receiving cotrimoxazole prophylaxis
This study is further discussed in a PLOS Medicine Perspective by Richard Steketee.
Information is available from the World Health Organization on malaria (in several languages) and on malaria in pregnancy; information on IPTp and the updated WHO policy recommendation on IPTp with SP are available; the 2013 World Malaria Report provides details of the current global malaria situation
The US Centers for Disease Control and Prevention also provides information on malaria; a personal story about malaria in pregnancy is available
Information is available from the Roll Back Malaria Partnership on all aspects of global malaria control, including information on malaria in pregnancy
The Malaria in Pregnancy Consortium is undertaking research into the prevention and treatment of malaria in pregnancy
MedlinePlus provides links to additional information on malaria (in English and Spanish)
doi:10.1371/journal.pmed.1001733
PMCID: PMC4172436  PMID: 25247709

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