Diabetic children often oblivious to hypoglycemia

Medical Tribune September 2009 P7

David Brill

Almost one in three children with type 1 diabetes cannot tell when their blood sugar dips low, and could face serious consequences from slipping into hypoglycemia, a study suggests.

A survey of 656 Australian children found that 29 percent had impaired awareness of hypoglycemia – a deficit in the adrenergic symptoms that ordinarily serve as a warning sign.

Children with impaired awareness were over twice as likely to have experienced a severe hypoglycemic episode in the previous year, involving loss of consciousness or seizure.

The effect was even more pronounced in the very young: children under 6 with impaired awareness were almost six times as likely to have had a serious episode.

Senior author Dr. Tim Jones said that hypoglycemia unawareness has traditionally been considered to be an adult problem, but urged physicians to step up screening among younger patients in light of the new findings.

“Ask the child: ‘do you get your usual symptoms? Do you still feel shaky when you go low? Or is the first thing you notice about being low that you find a low reading when you test yourself?’ It only takes a minute if you know what to ask,” he said.

Hypoglycemia unawareness appears to be caused by hypoglycemia itself, with repeated episodes successively dampening the adrenergic response, added Jones, head of the department of endocrinology and diabetes at Princess Margaret Hospital for Children, Perth, Australia.

The good news, however, is that the problem seems to some extent to be reversible, he said. Once impaired awareness is identified, the patient should meticulously ensure that they avoid hypoglycemia for around a month, and the warning symptoms may begin to return.

Further testing can also be carried out – particularly using continuous glucose monitoring systems to track a child’s blood sugar over time. This can help to identify and avoid episodes of hypoglycemia, regardless of whether the child is aware of it.

The study involved type 1 diabetic children aged from 6 months to 19 years. All were taking insulin – ranging from twice-daily injections to four times a day with insulin analogs and subcutaneous infusion therapy. [Diabetes Care 2009 Jul 8; Epub ahead of print]

A total of 161 hypoglycemic episodes had occurred in the year leading up to the study. The rate of episodes among children with impaired awareness was 37.1 episodes per 100 patient-years, compared to 19.3 per 100 patient-years in children with normal awareness.

Patients with impaired hypoglycemia awareness tended to be younger, had an earlier onset of diabetes, and had lower mean HbA1C levels since diabetes onset.

Questions raised over childhood antibiotics

Medical Tribune August 2009 SFV

David Brill

Using antibiotics to treat acute otitis media (AOM) in young children could increase their risk of recurrent infection, a recent study suggests.

Children who received amoxicillin for AOM were 2.5 times more likely to have a recurrent episode within the following 3.5 years, reported Dutch researchers, who are calling for more conservative use of antibiotics in this setting.

Senior author Dr. Maroeska Rovers said that up to 80 percent of children with mild, uncomplicated AOM will recover spontaneously, and that a 2 to 3 day “wait and see” policy is justified in such cases. Close observation by parents is required, since acute mastoiditis can result if AOM worsens and goes untreated, she said.

The British Medical Journal study included follow-up surveys from 168 children who had presented to Dutch GPs with AOM between the ages of 6 months and 2 years, and been randomized to amoxicillin or placebo. It is one of the first studies to look at the long-term effects of antibiotics in pediatric AOM, the authors say. [2009 Jun 30;338:b2525]

Sixty three percent of antibiotic-treated children had an AOM recurrence, compared to 43 percent of placebo-treated children (risk difference 20 percent; 95% CI 5-35%). Antibiotic-treated children were, however, less likely to undergo ear, nose and throat (ENT) surgery (21 percent versus 30 percent; risk difference 9 percent; 95% CI 4-23%).

Singapore expert Associate Professor Lynne Lim cautioned that more research is needed before practice should be changed, particularly given the small size of the study, the width of the reported confidence intervals and the different ethnicity and geographical location of patients.

“The debate on antibiotics use in AOM is continuing worldwide. It is definitely important to use antibiotics judiciously to avoid bacterial resistance and worse outcomes, if any, but until we are able to comcommitantly answer in the same study the complication rates and other problems associated with no antibiotic use, we cannot answer the question fully,” said Lim, head of the pediatric ENT service and senior consultant ENT surgeon at the National University Health System Singapore.

“The study suggests that more large, population-based, randomized clinical trials should be done to determine the cost-benefit of antibiotic use in AOM. I will continue treating as normal until more data are out,” she said, adding that that she typically follows US guidelines when treating AOM, and prescribes high-dose oral amoxicillin or amoxicillin/clavulanate potassium (80-90 mg/kg per day) for 7 to 10 days for children under 2.

Rovers, a clinical epidemiologist at University Medical Center Utrecht in the Netherlands, stressed that the “wait and see” policy should only apply to mild, unilateral AOM. Children under 2 years who have bilateral AOM or AOM with otorrhea should receive antibiotics without delay, she said, citing a meta-analysis of 1,643 children which found that antibiotics were of greatest benefit in these subgroups. [Lancet 2006 Oct 21;368(9545):1429-35]

“We now know which children benefit most from antibiotics but we also know that there is some harm. The next step for me will be to try to study the benefit and risk. Then we can say whether the guidelines should be changed or should not be changed,” she said.

Rovers and Lim both added that analgesics should be given to all children with AOM, regardless of whether antibiotics are prescribed.

Singapore center set to tackle childhood cancer in Asia

Medical Tribune April 2009 SFIV

David Brill

A new Singapore center could help raise childhood cancer survival rates across Asia, thanks to a recent $24 million funding boost.

The money will expand treatment facilities and strengthen research at the Viva-University Children’s Cancer Centre, which has already treated some 40 overseas children and begun training visiting specialists.

Around four out of five children with leukemia are cured in Singapore but in nearby countries this figure can be as low as one in 20.

“There is an urgent need for us to respond to the cries of children with cancer in Singapore and the whole region,” said Mrs. Jennifer Yeo, director and secretary of Singapore-based Viva Foundation for Children with Cancer.

“We are confident that with the support of all our donors, volunteers and strategic partners we can save many young lives,” she said.

The center, known as VUC3, has been operational for a year but was officially opened last month. Two specialists from the Philippines have already trained there, and one each from Myanmar and Brunei are currently in training.

The new funding comprises a $12 million gift from the Goh Foundation – a nonprofit private group – matched like-for-like by the Singapore government.

Four main research programs will be established, comprising bone marrow transplantation, childhood leukemia, bone cancer and ‘after completion of therapy,’ which focuses on the long-term impact of cancer treatment. This research will have a strong translational clinical focus with a view to raising cure rates, lowering treatment costs and minimizing side effects, said Associate Professor Allen Yeoh, medical director of VUC3.

“This will provide us with a quantum leap in the care of childhood cancer in Singapore, and help ensure that no child dies in the dawn of life. In the current severe recessionary climate, we are truly grateful to the Goh Foundation for their generosity,” said Yeoh, also a consultant at the University Children’s Medical Institute, National University Hospital, which houses VUC3.

Pediatric cancer survival is “dismal” in low-income countries, according to a study published last year. Five-year survival in the Philippines was estimated at 10 percent and in Vietnam just 5 percent. [Lancet Oncol 2008 Aug;9:721-9]

Between 120 and 140 new pediatric cancer cases are diagnosed in Singapore each year – some 40 percent of which are leukemia. Around 40 local children have been treated at VUC3 so far.

The center has already installed five new bone marrow transplant rooms and raised the number of inpatient beds from 12 to 17. The funding has also helped establish the Viva-Goh Foundation Professorship in Pediatric Oncology.

VUC3, built at a cost of $5 million from the Singapore Tote Board and Viva Foundation, is working closely with the St. Jude Children’s Research Hospital in Memphis, US – one of the world’s leading childhood cancer centers.

Greater awareness needed on childhood anxiety disorders

Medical Tribune March 2009 P5
David Brill

Pediatric anxiety disorders are “under-recognized and under-treated” and could be contributing to depression, drug abuse and educational underachievement in later life, a leading US psychiatrist has warned.

As many as 20 percent of children have some sort of anxiety problem but few are likely to be receiving optimal therapy, Professor Graham Emslie wrote in a recent New England Journal of Medicine editorial. [2008 Dec 25;359(26):2835-6]

Specialists at KK Women’s and Children’s Hospital (KKH) in Singapore, where referrals for pediatric anxiety disorders are low but rising, agreed that the problem is under-recognized and called for greater awareness among medical practitioners.

Emslie, a professor of psychiatry and pediatrics at the University of Texas Southwestern Medical Center, said that children often develop avoidance or coping strategies which can mask the true extent of the problem and contribute to the diagnosis being missed. Genuine anxiety disorders may also be dismissed as “normal, developmentally appropriate worries, fears and shyness,” he said.

The success of the CAMS* study, published in the same edition of the journal, highlights that the treatment options for pediatric anxiety are now more effective than ever before, Emslie said. The researchers found that 81 percent of children showed significant improvements in their anxiety levels when cognitive behavioral therapy (CBT) was combined with the selective serotonin-reuptake inhibitor sertraline. [N Engl J Med 2008 Dec 25;359(26):2753-66]

CBT is typically employed as the first line treatment at KKH but may also be combined with medications in severe cases, according to principal psychologist Ms. Frances Yeo. The number of children with anxiety disorders seen at the hospital rose from 26 in 2007 to 48 in 2008.

Yeo noted that the under-recognition of pediatric anxiety disorders may result from children’s inability to vocalize their worries and fears, which may subsequently manifest themselves as behavioral problems and lead to the child being wrongly labeled as lazy or difficult.

“Children usually show signs of their anxiety through physical symptoms such as stomachaches, headaches, hyperventilation, heart palpitations and tightness in the chest. These symptoms are rather vague and can overlap with many other disorders which make it difficult to distinguish,” she added.

“The first step for the medical community is awareness. GPs need to be alert for children with vague physical symptoms which cannot be explained by medical illnesses,” she said.

Pediatric anxiety disorders comprise a spectrum of conditions including social phobias, separation anxiety disorder, and generalized anxiety disorder. Children who are affected at ages 14 – 16 are more likely to have poor educational, mental health and social role outcomes at ages 16 – 21, a study of 1,265 New Zealand adolescents showed. [J Am Acad Child Adolesc Psychiatry 2001 Sep;40(9):1086-93]

Emslie noted that the exposure component seems to be the most effective part of CBT for children with avoidance strategies, suggesting that they should be encouraged to tackle their phobias head on. Doctors have an important role to play in this, he said, adding that they can unwittingly “collude” with avoidance coping by writing medical notes which give anxious children an excuse to miss school.

Dr. Ng Koon Hock, visiting consultant psychiatrist to the Mental Wellness Service at KKH, said that parents may be failing to recognize anxiety disorders because they tend to downplay a child’s emotions and focus overly on their behavior as a disciplinary issue. “There is less tendency to look at things from the child’s perspective,” he said.

Ng believes that doctors are generally reluctant to liberally grant medical leave to children who regularly makes suspicious-looking health complaints, but noted that this can be a difficult balancing act.

“If the child is very stressed and wants to escape from the problem then in the long-term it’s not helpful, but sometimes it does allow them to get by in the short term,” he said.

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*CAMS: Child-Adolescent Anxiety Multimodal Study

Beating childhood eating disorders: Mum’s the word

Medical Tribune December 2008 SFX

David Brill

Physicians can help children overcome eating disorders by taking a tactful, measured approach to worried mothers, an international expert said on a recent visit to Singapore.

Some 25 percent of children are thought to have a feeding disorder, the long-term consequences of which can include growth problems and an increased susceptibility to chronic diseases. [J Clin Gastroenterol 2000 Jan;30(1):34-46]

The majority of children, left to their own devices, will simply grow out of it, according to Dr. Benny Kerzner, a professor of pediatrics at the George Washington University School of Medicine, US. The problem, however, can be worsened if the parents’ minds are not put at ease.

"The trouble is the anxiety effect. These parents, even if their kids are doing nutritionally well, bring an intensity to their feeding which becomes a problem. The mothers are fearful and the resulting meal conflict has negative consequences."

It is common for mothers to be concerned about their child’s eating habits: a study by Abbott Nutrition shows that two in five consider their child to be a fussy eater, with 55 percent coaxing or enticing them to eat certain foods.

This anxiety is typically borne out of a fear that if the child is undernourished their development will be stunted, Kerzner said. Research shows, however, that psychosocial factors such as mother-child interactions actually have a greater impact than nutritional status on the cognitive development of toddlers with eating disorders. [Pediatrics 2004 May;113(5):e440-7]

Concerned mothers will often consult their GP or pediatrician, which provides the ideal opportunity to allay their fears, Kerzner said.

"The doctor needs to be empathetic, and needs to be certain that he’s not slighting the issue. You don’t want to make too much of a big deal out of it but you want to be knowledgeable enough to tell her why she can relax."

The doctor should begin by taking a thorough history in order to rule out genuine medical explanations such as allergies, pain with swallowing, or gastroesophageal reflux, Kerzner said.

"You’ll then be left with a large number of children where the mother is still concerned. Those I divide into two: the children who primarily have an appetite issue and, at the other end of the spectrum, the kids with sensory issues."

For children in the first group the doctor can teach some basic appetite-enhancing techniques or "food rules," such as stopping snacking between meals, limiting the size of meals, avoiding distractions at mealtimes and adopting a neutral attitude so that the child does not feel pressured to eat.

Sensory issues such as neophobia – the fear of new things – can be overcome by introducing new foods slowly and gradually, Kerzner said, adding that parents need to show genuine persistence and not lose heart if the child rejects a new food two or three times.

Doctors can also use growth charts to demonstrate to parents that their child is developing normally. In some cases they may also wish to recommend a dietary supplement or, if the problem persists, refer the child to a dietician, he said.

"In order to put them at ease you can’t fool them. What we need to have is a genuine discussion explaining the attitude that we have and why we’re not worried," Kerzner concluded. He was speaking at a press conference organized by Abbott Nutrition.

Paracetamol in infancy raises childhood asthma risk

Medical Tribune November 2008 SFXX
David Brill

Exposure to paracetamol during infancy could increase the subsequent risk of developing asthma, new research suggests.

Children aged 6 to 7 had a 46 percent increased risk of having asthma symptoms if they had received paracetamol for fever during their first year of life, data from the International Study of Asthma and Allergies in Childhood showed.

Use of the drug in infancy was also associated with an increased risk of rhinoconjunctivitis and eczema (odds ratios 1.48 and 1.35, respectively).

The authors of the Lancet study reviewed questionnaires completed by the parents or guardians of 205,487 children in 31 countries. [372(9643):1039-48]

“Because it was an epidemiological study we were unable to determine whether the relationship was causal … but when you put it together with all the other evidence we have it does suggest that paracetamol might be an important risk factor for the development of asthma,” said lead researcher Professor Richard Beasley, Medical Research Institute of New Zealand, Wellington.

Paracetamol should remain the preferred drug for relief of fever and pain in infancy but should be used sparingly, he said, noting that WHO guidelines recommend that the drug only be used for those with high fever (38.5°C or higher).

Beasley stressed that infants should not be switched to aspirin, which can cause the rare but potentially fatal Reye’s syndrome.

Current usage of paracetamol also increased the risk of asthma in a dose-dependent fashion. Children taking the drug on a regular basis were over three times as likely to have symptoms compared to those who were not taking it at all (odds ratio 3.23).

Dr. Chiang Wen Chin, an associate consultant in the department of pediatric allergy, immunology and rheumatology at KK Women’s and Children’s Hospital (KKH), Singapore, said that paracetamol use over the past 50 years has been safe and that the drug would remain first line for the majority of children (10mg/kg 4 to 6 hourly).

She added that ibuprofen can be given as a second line antipyretic, with tepid sponging also an option if the fever does not resolve.

Chiang noted, however, that there is a group of children who display angioedema and uticaria from high doses of paracetamol. [Pediatrics 2005 Nov;116(5):e675-80]

“We have demonstrated this in our own local patients that have presented to our clinic in KKH. Most of these children have allergic rhinitis, although not all of these have asthma,” she said.

“Our understanding of this pathophysiology is that paracetamol is a nonspecific COX-1 and COX-2 inhibitor, especially at high doses, and that this may result in a shunting of arachidonic acid production to predominantly leukotriene production, resulting in the release of various mediators such as mast cells and histamine release,” she said.

Beasley added that further studies – including randomized controlled trials of paracetamol in infancy – are needed to better understand the association with asthma.

The benefits of combining women’s and children’s healthcare

Medical Tribune August 2008 P2-3

Associate Professor Tay Eng-Hseon reflects on the advantages offered by centers such as KK Women’s and Children’s Hospital, Singapore

A mother and her child share a special relationship that begins even before birth. Having a combined hospital to attend to both of their needs provides continuity of care for the new family, and can help to develop and strengthen this bond. The ability to deliver specialist pediatric care on-site removes the potential need to separate a mother from her newborn baby within moments of delivery, enabling the family unit to remain intact within the same hospital. And as the child continues to grow, mothers can enjoy the convenience of having their own health needs attended to at the same place as those of their children. Joint visits such as this can help to reinforce the social support network and cohesion within a family.

Combining women’s and children’s healthcare is also beneficial from a medical standpoint as well as a social one. Delivery of crossover services becomes quicker, easier and more efficient within a single site. Many times at KK Women’s and Children’s Hospital (KKH) we have witnessed a neonatologist supervise the birth of a child before handing over to the pediatric urologist or cardiac surgeon, thereby allowing treatment to continue promptly without interruption or the need for further travel, with the associated delays and costs that this entails.

KKH treats a more specific section of the community than a general hospital, and this has proved to be beneficial from a practical point of view as well. With the field of potential patients narrowed we can reduce the range of equipment that we need, keep a more specific selection of drugs at the pharmacy, and standardize the hospital wards to a greater degree. We can also provide more specialized training for physicians, who can gain hands-on experience of a wide spectrum of conditions within their discipline.

Specializing in this way also has benefits for research, enabling a greater focus which in turn improves the ease of execution. Consequently KKH has participated in several large-scale international trials, including those of the rotavirus and cervical cancer vaccines. Entry into trials such as these can be competitive, but the ability to accrue large numbers of subjects quickly and easily has enabled our hospital to stay ahead of the competition. Furthermore we can provide a different patient perspective to centers in Europe and the US, and for these particular studies KKH was the main provider of Asian subjects.

Until 1997, pediatric hospital care in Singapore was spread between Tan Tock Seng, Singapore General and National University Hospitals. The visionary decision to consolidate these services into KKH – previously a dedicated women’s hospital – has enabled the hospital to expand into new areas and provide further dimensions of care to its patients. Examples include the development of highly specialized breast surgery and plastic and reconstructive surgery teams, and the opening of the Women Wellness Centre and Department of Child Development. Promoting mental health within the same vicinity as physical health also has the added benefit of reducing the stigma that can be associated with conventional psychiatric settings.

In a large specialist center such as KKH, the progression to higher-level services is a natural one, and it would not be surprising to see the private sector develop along these lines in future. High-end secondary and tertiary care such as this can only be feasible when there is access to a high volume of primary care patients, however, otherwise the demand will not match the capacity for supply and an expensive excess will develop.

In Singapore, patients from all corners of the country can reach the hospital within 30 minutes, making the concentration of care into one specialist centre very feasible. By virtue of its size and position within a dense population, KKH delivers a third of the 38,000-odd babies born each year in Singapore and provides care for around 80 percent of the country’s children. This model of centralized combined healthcare might not be feasible in all countries, however, and smaller hospitals in more sparsely-populated areas may not be able to match the volume of patients needed to sustain a dedicated center.

By focusing and centralizing our services we have been able to enhance our international reputation and provide regional leadership, and over the years we have attracted many foreign doctors on training fellowships. Other countries have begun looking into our model of hospital structure, and there has been a lot of interest from China in particular. For now women’s and children’s hospitals remain a rarity within Asia but, as KKH demonstrates, this system can provide many important benefits to both doctors and patients at all levels of care.