A New Technique for Fast and Safe Collection of Urine in Newborns

A New Technique for Fast and Safe Collection ofUrine in Newborns .pdf 

Earliest Sign of Autism: The Eyes May Have It

Deborah Brauser

November 14, 2013

Declining eye contact in infants as young as 2 months old may be one of the earliest indicators of autism spectrum disorder (ASD), new research suggests.

A prospective study, which followed 110 children from birth to age 3 years, showed that those who had a subsequent diagnosis of ASD started life with relatively normal attention to others' eyes. However, their eye fixation began to decline between the ages of 2 and 6 months and continued declining to study's end. This pattern was not observed in typically developing children.

"This study is really exciting to us because it gives us a new glimpse on autism that we hadn't seen before," lead author Warren Jones, PhD, director of research at the Marcus Autism Center With Children's Healthcare of Atlanta, Georgia, and Emory University School of Medicine, told Medscape Medical News.

"It has helped us to identify the earliest signs of autism that we've ever observed. And it gives us some proof that it's possible to identify these signs within the first months of life," said Dr. Warren.

The study was published online November 6 in Nature.

Prior Hypothesis Contradicted

Although deficits in eye contact have been a hallmark of autism, information on the onset of these problems has not been investigated before.

Infant's eye movements tracked as she watches a video of her mother. Image courtesy of Emory University.

"Unexpectedly, those early levels of eye looking seem to begin at normative levels," the researchers write. "This contradicts prior hypotheses of a congenital absence of social adaptive orientation and suggests instead that some social adaptive behaviors may initially be intact in newborns later diagnosed with ASD," they add.

Earlier this year, as reported by Medscape Medical News, researchers from Yale presented preliminary findings from a pilot study at a press briefing organized by the Brain and Behavior Research Foundation.

These results showed that brain activity, as recorded by electroencephalogram (EEG), after toddlers made eye contact was weaker for those with ASD compared with their normally developing counterparts.

In the current study, the investigators sought to explore the association between eye contact and ASD in a younger population.

"We were looking for precursor signs rather than the final manifestation of symptoms. For example, if we wait for the heart attack to happen, it's harder to make progress. Similarly, we were trying to look for mechanisms of typical social development and the way those mechanisms may not be developing in kids with autism," said Dr. Jones.

Dr. Warren Jones

The researchers enrolled 110 infants and divided them into 2 groups. The high-risk group consisted of those who had an older full sibling diagnosed with ASD (n = 59), whereas the low-risk group did not have any first-, second-, or third-degree relatives with ASD (n = 51).

At 10 different time points, when the children were between the ages of 2 and 24 months, eye movements were tracked as the infants watched videos of a caregiver. Percentage of time that a child fixated on the video caregiver's eyes, mouth, body, and nonhuman spaces was then calculated.

Results showed that 12 of the children (20.3%, 10 of whom were boys) in the high-risk group met diagnostic criteria for ASD by age 3 years vs just 1 child (a boy) in the low-risk group.

The investigators than compared the 11 boys with ASD with 25 boys from the low-risk group without ASD.

Steady Decline

After reviewing the eye-tracking data, the investigators found a steady decline in time spent looking at a caregiver's eyes in those with ASD. This decline began predominantly when the children were between age 2 and 6 months and continued to decline throughout the course of the study.

In contrast, when the typically developing children were between the ages of 2 and 6 months, they looked significantly more at the eyes than at any other area of the caregiver measured (P < .001).

At age 24 months, those with a later diagnosis of ASD focused on others' eyes half as long as children who did not develop ASD (P = .002).

This decline "was somewhat surprising," noted the researchers in a release. They added that a long-standing theory has been that social behaviors are completely missing in those with ASD. However, this study suggests that "social engagement skills are intact shortly after birth."

"This insight, the preservation of some early eye-looking, is important because in the future, if we were able to use similar technologies to identify early signs of social disability, we could then consider interventions to build on that early-looking and help reduce some of the associated disabilities that often accompany autism," added Dr. Jones.

He told Medscape Medical News, though, that parents and clinicians should not expect to see these differences in eye fixation by themselves.

"The signs we observed are only visible with the aid of sophisticated technology, and they required many measurements over many months," he explained.

"So the important take-away for parents is that if they have concerns, they should speak with their pediatricians and check out important links from the CDC [Centers for Disease Control and Prevention]."

Possibility of Earlier Intervention

"Autism isn't usually diagnosed until after age 2, when delays in a child's social behavior and language skills become apparent," Thomas R. Insel, MD, director of the National Institute of Mental Health (NIMH), said in a release.

However, he noted that this study showed that children "exhibit clear signs" of ASD at a much younger age than previously thought, which is a good thing for the field.

"The sooner we are able to identify early markers for autism, the more effective our treatment interventions can be," said Dr. Insel.

Dr. Jones added that his hope is that as he and his investigative team conduct more studies and enroll more families, in the event that these findings are replicated, they will lead to "real, viable tools for early detection in the future."

"More research is the next step. It showed us that it's possible to identify these signs. But now we want to understand what the extent of variability is on these signs in this population," he said.

The study was funded by grants from the NIMH and from the Simons Foundation. The study authors have disclosed no relevant financial relationships.

Nature. Published online November 6, 2013. Abstract

Can Adolescent Vaccination Reduce Infant Pertussis?

Can Adolescent Vaccination Reduce Infant Pertussis? CME/CE

News Author: Steven Fox
CME Author: Charles P. Vega, MD, FAAFP

CME/CE Released: 11/07/2013; Valid for credit through 11/07/2014

Clinical Context

Infants bear a disproportionate burden of morbidity and mortality from infection with pertussis, so a clear understanding of the primary sources of pertussis in this vulnerable age group is a public health priority. Bisgard and colleagues addressed this issue in a study published in the November 2004 issue of the Pediatric Infectious Disease Journal. They found that 75% of infant cases of pertussis were the result of contact with an infected family member, with the mother being the single most common source of familial transmission. Slightly more than half of primary source contacts with pertussis were adults, but 20% were between ages 10 and 19 years.

The recognition that adolescents are a significant source of pertussis led to recommendations in 2006 for universal vaccination of adolescents with the tetanus-diphtheria-acellular pertussis (Tdap) vaccine. By 2011, a total of 78% of adolescents had received Tdap. The current study by Auger and colleagues evaluates the effect of this effort on the rate of severe pertussis among infants.

Study Synopsis and Perspective

Widespread vaccination of adolescents against pertussis, spurred by 2006 recommendations from US health authorities, appears to have helped reduce pertussis-related hospitalizations among infants.

Katherine A. Auger, MD, from the Division of Hospital Medicine, Department of General Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Ohio, and colleagues, report the results of their study in an article published online October 21 in Pediatrics.

In 2006, the Centers for Disease Control and Prevention's (CDC's) Advisory Committee on Immunization Practices recommended universal administration of the Tdap vaccine to adolescents, who are a known source of pertussis in infants.

The recommendations have significantly improved vaccination rates among adolescents. By 2011, 78% of adolescents in the United States had received Tdap immunizations. "We sought to understand if patterns of pertussis hospitalization for infants changed with adoption of Tdap vaccination among adolescents," Dr. Auger and colleagues write.

Therefore, the investigators mined data from the Nationwide Inpatient Sample to identify infants younger than 1 year diagnosed with pertussis. They used data from 2000-2005 to estimate the rate of infants' hospitalizations if Tdap vaccinations had not increased in teenagers and compared those with observed hospitalization rates for 2008-2011. They excluded the 2 years immediately after the Advisory Committee on Immunization Practices recommendations (2006 and 2007) because the recommendations had not yet been widely implemented.

During 2000, the incidence of pertussis-related infant hospitalizations was 5.82 (95% confidence interval [CI], 4.51 - 7.13) discharges per 10,000 infants in the US population. "The rate increased during pre-Tdap years by a mean of 0.64 pertussis discharges per 10 000 infants per year (P for trend = .004)," the researchers note.

In contrast, after implementation, the observed rate was lower than the expected rate in 3 of 4 years examined. In 2008, the observed rate was 3.85 hospitalizations per 10,000 infants (95% CI, 2.90 - 4.81) compared with an expected rate of 10.09 (95% CI, 7.41 - 12.76). In 2009, the observed rate was 5.84 (95% CI, 4.41 - 7.27) vs an expected rate of 10.72 (95% CI, 7.63 - 13.82), and in 2011, the observed rate was 3.27 (95% CI, 2.37 - 4.16) vs an expected rate of 12.00 (95% CI, 8.06 - 15.94).

The exception to the pattern was 2010, in which there was no significant difference between the observed rate (7.78; 95% CI, 5.10 - 10.46) and the expected rate (11.36; 95% CI, 7.84 - 14.88).

The findings suggest that adolescent vaccination may help reduce the burden of severe infant pertussis cases that require hospitalization yet are not consistent enough to have mitigated infantile hospitalizations for pertussis in 2010, the first peak year of pertussis incidence after Tdap recommendations were published.

"Our findings of an inconsistent impact on infant pertussis hospitalizations in the Tdap era through 2011 indicate that infants may need further protection by 1 of 2 immunization efforts: improving vaccination rates among adolescents and implementing expanded vaccination recommendations among adults," the authors write.

Dr. Auger has received salary support from the Robert Wood Johnson Foundation through the Clinical Scholars Program. The other authors have disclosed no relevant financial relationships.

Pediatrics. Published online October 21, 2013. Abstract

Study Highlights

• Researchers used the Nationwide Inpatient Sample, the largest all-payer database of hospitalizations across the United States, to evaluate their study question. The researchers focused on children admitted to the hospital at age younger than 1 year with a diagnosis code for pertussis.
• Hospitalization rates for infants were compared in 2000-2005, when Tdap was not recommended for adolescents, with 2008-2011. By 2008, more than 40% of adolescents had received Tdap. Admissions from 2006 and 2007 were excluded because of the nascent implementation of Tdap vaccination for adolescents during these years.
• Researchers performed analyses that attempted to adjust for changes in the propensity of clinicians to admit infants with pertussis with time as well as changes in the prevalence of pertussis from year to year.
• The rate of hospitalizations for pertussis increased from 2001-2005, from 4.98 hospitalizations per 10,000 infants to 12.89 hospitalizations per 10,000 infants.
• The expected rate of hospitalizations was lower than expected in 2008, 2009, and 2011, with an actual rate of 3.27 to 5.84 hospitalizations per 10,000 infants.
• In 2010, the expected rate of hospitalizations (11.36 per 10,000 infants) was similar to the actual rate of hospitalization (7.78 per 10,000 infants).
• Overall, the rates of hospitalization for pertussis were lower than expected in 3 of the 4 years evaluated after adoption of the adolescent Tdap vaccine.
• Among infants who were hospitalized for pertussis, the mean age at the time of hospital discharge was 87 days. The mean length of hospital stay was 5.4 days, and 5.7% of infants were judged to have life-threatening pertussis infection.
• There was no evidence that pertussis vaccination among adolescents affected the percentage of admitted infants with life-threatening illness or the mean age of admitted infants.
• The researchers compared their rates of pertussis hospitalizations with the number of pertussis cases reported by the CDC to validate their data set. However, there were clearly years in which the number of cases in the current study either exceeded or was less than the number of cases from the CDC. The 2 data sets generally agreed on general trends in pertussis activity from year to year.

Clinical Implications

• A previous study by Bisgard and colleagues found that 75% of infant cases of pertussis were caused by contact with an infected family member.
• The current study by Auger and colleagues suggests that Tdap vaccination among adolescents may have a modest effect in reducing the risk for hospitalization for pertussis among infants.

Timing Is Everything in First Dose of Measles-Containing Vaccines

Timing Is Everything in First Dose of Measles-Containing Vaccines CME/CE

News Author: Diedtra Henderson
CME Author: Charles P. Vega, MD, FAAFP

CME/CE Released: 10/30/2013; Valid for credit through 10/30/2014

Clinical Context

Failure to fully vaccinate children is a serious public health concern, and an editorial by Feemster and Offit, which accompanies the current study, examines the phenomenon of undervaccination. They cite a recent study that describes the prevalence of missing at least 1 vaccination by the second birthday at 48.7% among US children. There are many reasons for undervaccination, but approximately 12% of these cases were due to parental choice to delay vaccination or outright refusal of vaccination.

Many parents refuse vaccines because of safety concerns, although delayed vaccination places the child at increased risk for infectious disease. However, scarce data exist regarding how a delayed vaccine schedule affects vaccine safety. The current study by Rowhani-Rahbar and colleagues fills this gap by focusing specifically on vaccines against measles.

Study Synopsis and Perspective

Infants who received vaccines containing live, attenuated measles were less likely to have a seizure within 7 to 10 days if the vaccination was administered at the recommended time, between ages 12 and 15 months, compared with older infants whose first measles dose was delayed, according to a large retrospective cohort study.

Ali Rowhani-Rahbar, MD, MPH, PhD, from the Kaiser Permanente Vaccine Study Center, Oakland, California, and coauthors published their results online October 14 in JAMA Pediatrics.

Two US Food and Drug Administration–approved vaccines containing live, attenuated measles are administered to American children: the measles, mumps, and rubella vaccine (MMR) and the MMR and varicella vaccine. The first shot of the 2-dose series is recommended to be given to infants between ages 12 and 15 months. Approximately 85% of infants receive the vaccination by age 19 months.

To examine the effect of infant age on the risk for vaccine-related fever and seizures, the researchers tapped the Vaccine Safety Datalink, a collaborative effort between the Centers for Disease Control and Prevention (CDC) and 10 managed care organizations. The database pools information on more than 9 million members and is used to track vaccine safety in the United States. The authors focused on the records of children between 12 and 23 months old who had received measles-containing vaccine between January 2001 and December 2011, including 840,348 infants.

"We found that the magnitude of increased risk of seizures following immunization with measles-containing vaccines during the second year of life depends on age," Dr. Rowhani-Rahbar and colleagues write. "While measles-containing vaccines administered at 12 to 15 months of age are associated with an increased risk of seizures 7 to 10 days following immunization [relative risk, 3.4 (95% confidence interval [CI], 3.0 - 3.9); attributable risk, 4.0 excess cases per 10,000 doses (95% CI, 3.4 - 4.6)], their delayed administration at 16 to 23 months of age may result in an even greater increased risk of that adverse event following immunization [relative risk, 6.5 (95% CI, 5.3 - 8.1); attributable risk, 9.5 excess cases per 10,000 doses (95% CI, 7.6 - 11.5)]."

In an accompanying editorial, Kristen A. Feemster, MD, MPH, MSHPR, and Paul Offit, MD, both from the Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, and the Division of Infectious Diseases and the Vaccine Education Center, The Children's Hospital of Philadelphia, called the study "significant."

"First, it reinforces the well-established safety of the current recommended schedule, which is based on many years of prelicensure and postlicensure safety and effectiveness data, including concomitant use studies," Dr. Feemster and Dr. Offit write.

"Second, this study provides an example of the potential for current vaccine safety surveillance mechanisms to identify outcomes associated with alternate vaccine schedules."

Dr. Rowhani-Rahbar and colleagues note that a possible reason for the differing risk profiles is the ability of immune systems of 16- to 23-month-olds to mount a more rigorous response to the measles vaccine, compared with younger infants.

"Vaccines are typically recommended at an age that maximizes the likelihood of vaccine-induced protection and minimizes the risk of morbidity and mortality that would occur by delaying immunization. The safety profile of vaccines at different ages is another important consideration in immunization policy decision making," the authors conclude.

Support for this study was provided by the CDC. Nine of the 13 study authors have received institutional research support from the CDC, and 1 study author has disclosed being employed by the CDC. In addition, 1 coauthor has received institutional research support from GlaxoSmithKline; 1 coauthor, from MedImmune; 1 coauthor, from Merck & Co; 1 coauthor, from the National Institutes of Health, Novartis, Pfizer, and sanofi-pasteur; and 2 coauthors, from Merck & Co, Novartis, GlaxoSmithKline, Pfizer, and sanofi-pasteur. The remaining study authors and editorialists have disclosed no relevant financial relationships.

JAMA Pediatr. Published online October 14, 2013. Abstract

Study Highlights

• Researchers used data from the Vaccine Safety Datalink to determine the effect of age of administration of measles-containing vaccines on the rate of febrile seizures. This database includes information on more than 9 million members annually.
• Specifically, the study population included children between 12 and 23 months old who received vaccinations between 2001 and 2011.
• The main study outcomes were diagnosis codes for either fever or seizure in the 42 days after vaccination. The period from 7 to 10 days after vaccination was considered the major at-risk time for these outcomes. The remainder of the 42-day observation period served as a control.
• Researchers compared the rates of fever and seizures after vaccination among children ages 12 to 15 months vs ages 16 to 23 months. They also evaluated whether the addition of the varicella vaccine to the MMR vaccine as a combination vaccine affected the rate of febrile seizures.
• A total of 840,348 children provided data for study analysis. 51% of children were boys. The most commonly administered vaccine was MMR with varicella as a separate injection, and most vaccines were delivered at ages 12 to 13 months.
• There were 18,403 fever events after vaccination, 32.2% of which occurred 7 to 10 days after vaccination.
• There were 1810 seizure events after vaccination, 28.7% of which occurred 7 to 10 days after vaccination.
• The incidence rate ratios in comparing the at-risk time vs the control period for fever after vaccination were 4.4 and 5.9 among 12- to 15-month-old children and 16- to 23-month-old children, respectively. This difference was significant, but the attributable risk for excess fever associated with older age was not.
• Similarly, the relative risk for seizures was significantly higher among 16- to 23-month-old children (6.5; 95% CI, 5.3 - 8.1) compared with 12- to 15-month-old children (3.4; 95% CI, 3.0 - 3.9). Vaccination after age 15 months resulted in 9.5 excess cases of seizure compared with earlier vaccination (4.0 excess cases); this result was significant.
• The MMR vaccine, which included varicella as well in a single injection, was associated with a significant increase in the rates of fever (40%) and seizures (approximately 100%) compared with MMR with or without varicella as a separate injection.
• The higher rates of fever and seizures associated with the use of the combined MMR-varicella vaccine did not vary based on the child's age.

Clinical Implications

• The rate of undervaccination of children younger than 2 years is nearly 50% in the United States, and approximately 12% of cases of undervaccination are caused by parental choice against vaccines.
• The current study by Rowhani-Rahbar and colleagues demonstrates that the risk for seizures is higher when measles-containing vaccines are administered at ages 16 to 23 months vs ages 12 to 15 months. The rate of fever after vaccination was also higher among older children, and the use of the combined MMR-varicella vaccine was associated with higher risks for fever and seizures.

Provider Approach to Parental Resistance to Childhood Vaccination: What Works Best?

Provider Approach to Parental Resistance to Childhood Vaccination: What Works Best? CME

News Author: Troy Brown, RN
CME Author: Charles P. Vega, MD, FAAFP

CME Released: 11/13/2013; Valid for credit through 11/13/2014

Clinical Context

More parents are refusing or delaying childhood vaccines, which constitutes a significant public health problem. A study by Kempe and colleagues, which appeared in the May 2011 issue of the American Journal of Preventive Medicine, evaluated this phenomenon. Only 8% of providers surveyed reported rates of vaccine refusal in their practice of 10% or more, but 1 in 5 providers reported that at least 10% of parents requested to delay scheduled vaccines for children. More than half of providers reported taking at least 10 minutes to counsel families with vaccine concerns, and nearly two thirds of providers acquiesced to requests to delay vaccines. Providers believed that personal stories about what they would do for their own children were most effective in convincing parents to vaccinate their offspring.

Given this background, how do most clinicians approach the subject of vaccinating children, and are certain communication styles more effective in reducing parental resistance toward vaccination? The current study by Opel and colleagues examines this issue.

Study Synopsis and Perspective

The approach a clinician uses to discuss vaccinations plays a significant role in whether or not parents choose to have their child vaccinated at that visit, according to across-sectional observational study in which 111 provider–parent vaccine discussions during health supervision visits were recorded and analyzed.

Douglas J. Opel, MD, MPH, an assistant professor in the Division of Bioethics and the Division of General Pediatrics, Department of Pediatrics, University of Washington School of Medicine, Seattle, and at the Treuman Katz Center for Pediatric Bioethics at Seattle Children's Hospital, Seattle Children's Research Institute, Seattle, Washington, and colleagues report their findings in an article published online November 4 in Pediatrics.

"Although the linguistic format of how a topic is introduced has received attention in other medical settings, it has not yet been explored in the context of vaccine discussions," the authors write.

The study included parents of children aged 1 to 19 months who were screened with the Parent Attitudes about Childhood Vaccines survey. Vaccine-hesitant parents (VHPs) were defined as those having a score of 50 or higher. The researchers developed a coding scheme of 15 communication practices and applied it to all patient encounters.

A provider was using a presumptive format when he or she presumed that the parent would be willing to have the child vaccinated that day (eg, "Well, we have to do some shots"). Providers who used a participatory linguistic format (eg, "What do you want to do about shots?" "Are we going to do shots today?") gave the parent more decision-making latitude.

In multivariate logistic regression analyses, the researchers controlled for parental hesitancy status and demographic and visit characteristics.

A total of 111 vaccine discussions took place among 16 providers from 9 practices, half of which included VHPs. Three fourths (74%) of providers began vaccine recommendations with presumptive vs participatory formats.

Among the parents who were resistant to provider initiation (41%), a significantly higher number were VHPs than non-VHPs. Parents were significantly more likely to resist vaccine recommendations if the provider used a participatory instead of a presumptive initiation format (adjusted odds ratio, 17.5; 95% confidence interval, 1.2 - 253.5).

Half of the providers handled parental resistance by repeating their original recommendations (eg, "He really needs these shots"), and when that happened, almost half (47%) of parents who were initially resistant then accepted those recommendations.

Longitudinal studies will need to be conducted with a more diverse population of parents and healthcare providers, the researchers note.

"How providers initiate their vaccine recommendations at health supervision visits appears to be an important determinant of parent resistance to that recommendation," the authors write. "[I]f providers continue to pursue their original recommendation after encountering parental resistance, many parents eventually agree to it," they conclude.

The authors have disclosed no relevant financial relationships.

Pediatrics. Published online November 4, 2013.

Study Highlights

• Study data were drawn from a practice-based research group in Seattle, Washington. Researchers focused on preventive visits for children between ages 1 and 19 months. All visits occurred in 2011 and 2012.
• Parents were asked to complete the Parent Attitudes about Childhood Vaccine survey, which identifies VHPs.
• The preventive health visits were recorded and were fully transcribed. Experts in conversation analysis assessed provider communication and patterns of parent resistance. Specifically, researchers were interested in whether certain communication styles were associated with higher parental resistance to vaccination.
• 16 pediatric providers participated in the study, and researchers evaluated a total of 111 patient visits. Most participating parents were married, white mothers who were at least 30 years old and had an annual household income in excess of $75,000.
• The researchers purposefully oversampled VHPs, who constituted half of the study sample. 41% of parents voiced resistance to vaccines during the interview, with the majority of these parents explicitly rejecting the provider's recommendations.
• 74% of providers initiated the discussion of vaccines with presumptive statements, essentially telling the parent what was going to be done on this visit.
• However, providers were more likely to use a participatory invitation to consider vaccines when speaking with a VHP.
• 83% of parents resisted vaccine recommendations when providers used a participatory format to discuss vaccines, whereas only 26% of parents resisted a presumptive communication style on the part of the provider. The adjusted odds ratio for parental resistance associated with a participatory vs presumptive style was 17.5 (95% confidence interval, 1.2 - 253.5).
• When faced with parental resistance, half of providers persisted with their recommendations for vaccination, regardless of whether the parent was a VHP.
• 47% of parents who were initially resistant to vaccination accepted the provider's recommendation after persistent recommendations to vaccinate.

Clinical Implications

• In a previous study by Kempe and colleagues, providers believed that personal stories about what they would do for their own children were most effective in convincing parents to vaccinate their children.
• In the current study by Opel and colleagues, a presumptive communication style vs a participatory style on the part of the provider appeared to decrease parental resistance to childhood vaccination.

CME Test

Kids' Coughs, Colds May Last Weeks but Don't Need Drugs

December 17, 2013

By Genevra Pittman

NEW YORK (Reuters Health) Dec 17 - Children's coughs and colds can last up to two or three weeks and earaches may take a week to get better, according to a new review of past studies.

Researchers said they hope the findings help reassure both doctors and parents that respiratory symptoms can last "longer than previously appreciated" but typically don't require treatment.

"A lot of times, we just have to give it a bit more time," Dr. Sharon B. Meropol said.

Meropol, from Rainbow Babies and Children's Hospital and Case Western Reserve University School of Medicine in Cleveland, was not involved in the new research.

She said the findings are consistent with what she sees as a pediatrician.

For their review, Dr. Matthew Thompson from the University of Washington in Seattle and his colleagues analyzed the results of 48 studies of children with a respiratory tract infection.

Kids in those studies were treated with over-the-counter medicines, drug-free placebo pills or nothing. Researchers followed them to see when their symptoms went away.

Among children with earaches, 90% were better within seven to eight days of visiting a primary care doctor or the emergency room. Most kids with the common cold were better after 15 days, while it took 25 days for almost all children with a cough to be fully recovered.

Sore throats typically lasted anywhere from two to seven days, depending on the study.

The duration of earaches and common colds in particular was "considerably longer" than parents in the U.S. and UK are generally told, the researchers wrote in the British Medical Journal, online December 11.

Meropol said most children with coughs, colds and other respiratory tract infections don't need to see a doctor. With the exception of strep throat, those infections are typically caused by viruses.

"Some people . . . think that if symptoms go on past a couple of days, the child needs antibiotics," Meropol said. But viruses don't respond to antibiotics, and the drugs may cause diarrhea or other side effects among children.

What's more, using antibiotics could have long-term implications by increasing the chance that bugs become resistant to the drugs, making future infections harder to treat.

"The take home message is that symptoms of many of these common respiratory tract infections may last a while and that prolonged symptoms do not necessarily mean that the child needs antibiotics or other medications," Dr. Theoklis Zaoutis told Reuters Health in an email.

Zaoutis is an infectious diseases specialist at the Children's Hospital of Philadelphia in Pennsylvania and wasn't involved in the new review.

There are still some situations when children with respiratory symptoms do need to see a doctor, Meropol said.

That's when their symptoms keep getting worse, or don't start slowly getting better over time as expected. Kids who are having trouble breathing or have other serious symptoms also need to go to the doctor, she said.

SOURCE: http://bit.ly/J2NQ4A

BMJ 2013.

Bartlett's 2013 Review: Advances in the Highly Kinetic Field of Infectious Diseases

John G. Bartlett, MD

December 05, 2013

Editor's Note:
Medscape asked John G. Bartlett, MD, Professor Emeritus, Johns Hopkins University School of Medicine, to offer his review of the most important and practice changing advances in infectious disease in 2013.

Resistance to Antibiotics

No National Plan

The topic of antibiotic resistance needs no introduction. It is well known and has been declared a crisis by the World Health Organization, the Institute of Medicine (IOM), the Infectious Diseases Society of America, and the US Congress.

The United States has no national plan to deal with antibiotic resistance, despite recognition of the crisis for more than a decade.^[1] By contrast, the European Union has been systematically collecting data on antibiotic use and resistance by specific pathogens for 26 countries for 15 years and now has a 12-point plan and budget to address the problem in a coordinated fashion.^[2]

India is the source of many resistant microbes that have become global concerns, largely through air travel, including the infamous New Delhi strain of carbapenemase-producing Klebsiella pneumoniae (KPC). India has announced plans for a coordinated national attack on this problem, despite incredible economic and health challenges.

To reiterate, it is humbling that the United States has nearly 50% of the global budget for antibiotics, a crisis of abuse, and no plan to deal with what many feel is a looming disaster in modern medical care with the "postantibiotic era."

Resistance Priorities

The Centers for Disease Control and Prevention (CDC) recently published a massive scholarly review^[3] (see Antibiotic Resistance: The Big Picture) of antibiotic resistance in the United States and has defined the priorities (but without a plan). The 3 top priorities, which are described as "urgent," may surprise you: carbapenemase-producing Enterobacteriaceae, Clostridium difficile, and antibiotic-resistant Neisseria gonorrhoeae.

The devastating impact of KPC is well illustrated by the experience at the National Institutes of Health (NIH) Clinical Center, with 18 cases and 6 deaths during a 6-month period.^[4] Control was eventually achieved by building a wall to isolate patients with this pathogen, vaporizing rooms with hydrogen peroxide, ripping out plumbing when the agent was found in sinks, obtaining rectal swabs from all patients twice weekly to detect KPC carriage, whole-gene sequencing to determine transmission patterns, banning of cell phones and pagers, standardized handwashing (2 squirts with a 20-second scrub), and antiseptic baths for all patients.^[4,5]

The painful messages from these experiences are that once these "bad bugs" become established in a facility, draconian changes in medical care may be necessary at a high cost; referral facilities may reject patient transfers; and the publicity can be very damaging for the facility's image, as well as present liability risks.

Colistin

The problem of resistance and the paucity of new antibiotics has led to the scrambling for a "Hail Mary" to treat nearly pan-resistant gram-negative infections. Many clinicians have been looking to colistin or polymyxin, related drugs that were US Food and Drug Administration (FDA)-approved in 1961. These are the only active drugs for many highly resistant gram-negative bacteria, but data on their use are modest, dosing recommendations in the package inserts appear to be outdated, there is the perceived need for a companion antibiotic for "heteroresistance," and toxicity is common.^[6]

One study reported a 60% rate of nephrotoxicity with currently recommended dosing.^[7] This experience highlights the desperate need for new antibiotics.

New Tests, New Pathogens, and MERS-CoV

The New Microbiology Lab

Microbiology is in the process of a veritable sea change, with a shift from methods first used in 1850 -- a culture medium produced from seaweed (agar) -- to molecular methods for pathogen detection that are rapidly being introduced.^[8] The FDA has now approved nucleic acid amplification tests (NAATs) for multiple viruses (measles, mumps, human metapneumovirus, rhinovirus, coronavirus, enterovirus, adenovirus, respiratory syncytial virus, influenza, West Nile virus, herpes simplex virus, human papillomavirus, rabies virus, and cytomegalovirus). Bacteria for which NAATs are now approved include N gonorrhoeae; Chlamydia trachomatis; Mycoplasma pneumoniae; Legionella species; C difficile; Coxiella species; Borrelia burgdorferi; Ehrlichia species; Mycobacterium tuberculosis; and group A, B, C, and G streptococcus. None of these organisms should normally be found, so their presence usually indicates disease.

The bacteria that are most commonly encountered in clinical care, such as pneumococcus and Escherichia coli, are far more challenging, because they are so frequently part of the commensal flora. This makes meaningful detection appropriate only with quantitation or recovery from a normally sterile site, such as blood, pleural fluid, or biopsy specimens. This technology is now being used with blood cultures. The great advantage here is rapid detection (1-2 hours instead of the 36-48 hours required with conventional cultures) and the extraordinary sensitivity and specificity of this method. This must be viewed as possibly the biggest advance in microbiology in 150 years, but stewardship and interpretation of results will be critical.

New Pathogens

The field of infectious diseases is somewhat unique in the regular discovery of previously unknown pathogens, such as Legionella pneumophila (1978), HIV (1983), B burgdorferi (1983), and Helicobacter pylori (1986). Some examples of recent new pathogen discoveries include:

• Mimivirus: a giant gram-positive virus that appears to be a rare cause of pneumonia^[9];

• Borrelia miyamotoi: a tick-borne spirochete that causes a Lyme disease-like illness, found primarily in southern England, detected with serology and treated with doxycycline^[10];

• Emmonsia: a newly detected dimorphic fungus found to cause disseminated infection with prominent skin lesions in 13 patients with late-stage AIDS in South Africa^[11];and

• Bradyrhizobium enterica, which causes cord colitis syndrome in stem cell transplant recipients.^[12]

The Emergence of MERS-CoV

Middle East respiratory syndrome coronavirus (MERS-CoV) is the newly recognized pathogenic coronavirus that was originally identified in the Middle East and has reportedly infected 138 people and caused 60 deaths (43%).^[13] Of importance are the observations that person-to-person transmission has been shown and cases have been detected outside the original epidemic area, including Europe, but not yet in the United States. Nevertheless, there is great concern that this virus, a coronavirus with a bat heritage similar to that of severe acute respiratory syndrome (SARS), will behave like SARS, with global spread.

Thus, warnings have been made for detection, reporting, and isolation of patients who have unexplained severe respiratory infections and recent travel to the Arabian Peninsula or contact with a patient with this travel history. The CDC has distributed a diagnostic test; there is no effective antiviral therapy.

A major reason for this concern is the experience with SARS (also a coronavirus), which infected more than 8000 people and caused 770 deaths. The history of SARS was that it remained a localized infection in mainland China, until there was the infamous "super-spreader"-- the physician who traveled from Guangdong province to Hong Kong; stayed in room 911 of the Metropole Hotel; and apparently became the source of epidemics in Canada, Vietnam, Singapore, and Hong Kong.^[14] Newer thinking discounts the concept of a single person as a "super-spreader," however, and the terminology has been changed to a "super-spreader environment," because the notion that a single patient could produce such devastation is biologically implausible.

Epidemics

A characteristic feature of the infectious diseases discipline is the continuing experience with epidemics. We have learned that they will occur; we just don't know when, where, with what, and how bad they will be. The highlights of 2013 are in 3 categories.

Pediatric Infections

Pediatric infections include measles (which caused 159 cases of a disease that was believed to be eradicated in 2000) and pertussis, with 41,880 reported cases so far in 2013.^[15] A big difference between these 2 infections is that most patients with measles are unvaccinated persons, whereas pertussis cases occurred primarily in persons who had received the vaccine, calling attention to the inadequacy of our pertussis vaccine strategy. Despite the noise from antivaccine proponents, vaccination refusal for pediatric patients in 2012-2013 in the United States was only 1.8%, substantially lower than many thought.

Foodborne Outbreaks

Foodborne outbreaks occur regularly and, so far in 2013, have included Listeria from contaminated cantaloupes traced to a Colorado farm, which resulted in143 hospitalizations and 33 deaths.^[16] There was also an outbreak of Salmonella enterica from contaminated turkey, with 278 infected patients and 1 death involving 28 states. This is not surprising, because Salmonella is the most common cause of food epidemics,^[17] but in this case the implicated strain was resistant to several antibiotics thought to reflect the use or abuse of antibiotics in agriculture -- the "farm to fork" concern in the resistance issue.

The massive geographic spread of foodborne infections from a single source represents the switch from nearby farms as food sources to the massive distribution system that permits exposure to thousands of individuals at distant sites. This could be easily controlled with food irradiation, which is endorsed by the IOM, FDA, CDC, and other reliable sources, but is rejected by consumers because of the perception that irradiation causes cancer.

Fungal Infections

The infamous fungal meningitis outbreak in 2013 that resulted in 741 cases and 55 deaths in 18 states exposed a huge gap in quality assurance policies in the United States.^[18] There are 7500 compounding pharmacies in the United States, and these are not subject to requirements for showing safety, efficacy, or even correct dose labeling. At least 3 outbreaks of meningitis have been traced to compounding pharmacies since 2001, so it is clearly time for action.

Influenza

Influenza continues to be a humbling infectious disease, as shown by swine H1N1 influenza. Extensive experience with influenza shows that new epidemic strains come from Asia in the winter, but this influenza virus defied history because it came from the Western Hemisphere during the summer -- a complete surprise to experts in the field. The uniqueness of the strain was detected by molecular analysis of a sample from a child with flu at a military base in San Diego.

The greatest contemporary influenza concerns are H5N1 and H7N9.^[19,20] Recent reports show that H5N1 has been recognized for 16 years; there have been about 733 reported cases, with a mortality rate of 59%. H7N9 reports indicate that about 133 cases have occurred, with a mortality of 28%. Birds are the natural hosts for both agents, but there is a big difference: H5N1 infection is fatal in birds, whereas H7N9 infection is asymptomatic in birds, making elimination of the source virtually impossible.

Influenza will remain a priority health concern for the indefinite future, on the basis of our morbid experience with pandemics and our admittedly suboptimal antiviral medications and vaccines. H5N1 and H7N9 could easily be global epidemics based, in part, on our humbling experience in what we know from swine flu.

The Microbiome

This possibly is the most exciting news story in the field, although now in the nascence of knowledge and practical application. Articles on the microbiome stem from a large, multicenter, NIH-sponsored study using molecular methods (16S ribosomal RNA) to define the flora at 15 anatomical sites in 300 persons.^[21-23] This work now has produced 35 billion "reads"(a term that describes counting the number of microbes reported in the NIH network of microbiome centers.) Important principles include the facts that the cellular composition of humans is 90% "them," each anatomical site and individual has unique flora, antibiotics have a major impact on these flora, and certain patterns are associated with different disease states.

At this juncture, it seems clear that study of the microbiome will open new doors to concepts in pathogenesis of common pathologic conditions, such as cardiovascular disease, allergies, obesity, inflammatory bowel disease, cancer, and diabetes. Our understanding of this process will require a departure from the age-old Koch postulates of the single pathogen causing the disease. Instead, the focus will be on communities of communicating organisms.

It now seems clear that this work could change fundamental concepts of common diseases and suggests that antibiotics and probiotics might be used to prevent or treat multiple conditions not considered to be infectious diseases as conventionally defined. For example, studies in rodents show that antibiotics may alter risk for cardiovascular disease, and early studies show promise that this is applicable to humans as well.^[22] The use of stool transplants to control relapsing C difficile infection (CDI) is a well-established use of this concept, as described below.

Clostridium difficile infection

CDI is listed as 1 of the 3 major microbial threats in the United States in the CDC resistance review^[1] as a result of escalating rates, with an estimated 250,000 cases and 14,000 deaths yearly in the United States. Important new developments in the past 2-3 years are:

• The introduction of fidaxomicin^[24] as the second FDA-approved drug for treatment, with the significant benefit compared with oral vancomycin of reduced frequency of relapses;

• The fascinating, if impractical, use of a beagle "sniff test" as a near-perfect diagnostic method^[25];

• The diverting ileostomy as a new method of surgery for refractory cases, with the advantages of substantial reduction in surgical mortality plus colon preservation^[26];

• New epidemiologic data based on whole-gene analysis showing that the major method for prevention favors antibiotic control over infection control^[27];and

• The burst of enthusiasm for treatment of relapsing CDI with stool transplants, a practical use of the microbiome, that has been used with good success since 1958.^[28]

The stool transplant procedure can be done with delivery of donor stool specimens by nasogastric tube, enema, or colonoscopy, but Dr. Tom Louie recently presented good results with fresh donor specimens delivered in 24-34 oral pellets.^[29] Lingering questions are the issue of use of stool as a drug requiring a "treatment IND" (investigational new drug application to the FDA) and stool transplantation as a billable procedure. (Dr. Louie does this without charge in the patient's home.)

References

1. Bartlett JG, Gilbert DN, Spellberg B. Seven ways to preserve the miracle of antibiotics. Clin Infect Dis. 2013;56:1445-1450. Abstract
2. Watson R. Europe launches 12 point plan to tackle antimicrobial resistance. BMJ 2011;343:d7528.
3. Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2013. September 16, 2013. www.cdc.gov/drugresistance/threat-report-2013/ Accessed November 20, 2013.
4. Snitkin ES, Zelazny AM, Thomas PJ, et al. Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing. Sci Transl Med. 2012;4:148ra116.
5. Palmore TN, Henderson DK. Managing transmission of carbapenem-resistant enterobacteriaceae in healthcare settings: a view from the trenches. Clin Infect Dis. 2013;57:1593-1599. Abstract
6. Velkov T, Roberts KD, Nation RL, Thompson PE, Li J. Pharmacology of polymyxins: new insights into an 'old' class of antibiotics. Future Microbiol. 2013;8:711-724. Abstract
7. Kubin CJ, Ellman TM, Phadke V, Haynes LJ, Calfee DP, Yin MT. Incidence and predictors of acute kidney injury associated with intravenous polymyxin B therapy. J Infect. 2012;65:80-87. Abstract
8. Caliendo AM, Gilbert DN, Ginocchio CC, et al; Infectious Diseases Society of America (IDSA). Better tests, better care: improved diagnostics for infectious diseases. Clin Infect Dis. 2013;57(Suppl 3):S139-S170. Abstract
9. Saadi H, Pagnier I, Colson P, et al. First isolation of mimivirus in a patient with pneumonia. Clin Infect Dis. 2013;57:e127-e134. Abstract
10. Gugliotta JL, Goethert HK, Berardi VP, Telford SR 3rd. Meningoencephalitis from Borrelia miyamotoi in an immunocompromised patient. N Engl J Med. 2013;368:240-245. Abstract
11. Kenyon C, Bonorchis K, Corcoran C, et al. A dimorphic fungus causing disseminated infection in South Africa. N Engl J Med. 2013;369:1416-1424. Abstract
12. Bhatt AS, Marty FM, Meyerson M. Bradyrhizobium enterica in cord colitis syndrome. N Engl J Med. 2013;369:1867.
13. Memish ZA, Al-Tawfiq JA, Assiri A. Hospital-associated Middle East respiratory syndrome coronavirus infections. N Engl J Med. 2013;369:1761-1762.
14. Horby PW, Pfeiffer D, Oshitani H. Prospects for emerging infections in East and southeast Asia 10 years after severe acute respiratory syndrome. Emerg Infect Dis. 2013;19:853-860. Abstract
15. Auger KA, Patrick SW, Davis MM. Infant hospitalizations for pertussis before and after Tdap recommendations for adolescents. Pediatrics. 2013;132:e1149-e1155. Abstract
16. McCollum JT, Cronquist AB, Silk BJ, et al. Multistate outbreak of listeriosis associated with cantaloupe. N Engl J Med. 2013;369:944-953. Abstract
17. Gould LH, Walsh KA, Vieira AI, et al; Centers for Disease Control and Prevention. Surveillance for foodborne disease outbreaks -- United States, 1998-2008. MMWR Surveill Summ. 2013;62:1-34.
18. Chiller TM, Roy M, Nguyen D, et al; Multistate Fungal Infection Clinical Investigation Team. Clinical findings for fungal infections caused by methylprednisolone injections. N Engl J Med. 2013;369:1610-1619. Abstract
19. Gao HN, Lu HZ, Cao B, et al. Clinical findings in 111 cases of influenza A (H7N9) virus infection. N Engl J Med. 2013;368:2277-2285. Abstract
20. Morens DM, Taubenberger JK, Fauci AS. Pandemic influenza viruses -- hoping for the road not taken. N Engl J Med. 2013;368:2345-2348. Abstract
21. Blaser M, Bork P, Fraser C, Knight R, Wang J. The microbiome explored: recent insights and future challenges. Nat Rev Microbiol. 2013;11:213-217. Abstract
22. Tang WH, Wang Z, Levison BS, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368:1575-1584.Abstract
23. Slashinski MJ, Whitney SN, Achenbaum LS, Keitel WA, McCurdy SA, McGuire AL. Investigators' perspectives on translating human microbiome research into clinical practice. Public Health Genomics. 2013;16:127-133. Abstract
24. Louie TJ, Miller MA, Mullane KM, et al; PT-80-003 Clinical Study Group. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364:422-431. Abstract
25. Bomers MK, van Agtmael MA, Luik H, van Veen MC, Vandenbroucke-Grauls CM, Smulders YM. Using a dog's superior olfactory sensitivity to identify Clostridium difficile in stools and patients: proof of principle study. BMJ. 2012;345:e7396.
26. Neal MD, Alverdy JC, Hall DE, Simmons RL, Zuckerbraun BS. Diverting loop ileostomy and colonic lavage: an alternative to total abdominal colectomy for treatment of severe, complicated Clostridium difficile associated disease. Ann Surg. 2011;254:423-427. Abstract
27. Eyre DW, Cule ML, Wilson DJ, et al. Diverse sources of C. difficile infection identified on whole-genome sequencing. N Engl J Med. 2013;369:1195-1205.Abstract
28. Borody TJ, Brandt LJ, Paramsothy S, Agrawal G. Fecal microbiota transplantation: a new standard treatment option for Clostridium difficile infection. Expert Rev Anti Infect Ther. 2013;11:447-449. Abstract
29. Louie T, Cannon K, O'Grady H, Wu K, Ward L. Fecal microbiome by oral fecal microbial capsules for recurrent Clostridium difficile infection (rCDI). Program and abstracts of the Infectious Diseases Society of America ID Week 2013; October 2-6, 2013; San Francisco, California. Abstract 89.