Your Family Physician

NEW YORK (Reuters Health) May 18 - Comprehensive inpatient treatment is effective in the majority of patients with refractory chronic daily headache, according to findings published in the April issue of Headache.

"An evidence-based assessment (2004) concluded that many intractable headache patients benefit from inpatient treatment, and underscored the need for more research, including identification of outcome predictors," Dr. Alvin E. Lake III, and colleagues from Michigan Head-Pain and Neurological Institute, Ann Arbor, write.

The program included intravenous and oral medication programs, withdrawal from overused medications, cognitive behavioral therapy and psychoeducational groups. When needed, patients also received interventional anesthesiology, physical and occupational therapy, and consultation for comorbid conditions. The mean length of stay in the inpatient program was 13 days. Outcome measures included patient-reported pain levels and consensus of medical staff.

A total of 267 patients (212 women and 55 men) from 43 states and Canada completed the program. The mean age of the subjects was 40.3 years. The modal primary diagnosis was intractable chronic daily headache, predominantly migraine (n = 226).

Overall, 158 patients met the criteria for medication overuse headache, primarily involving opioids (n = 127), followed by triptans (n = 39) and ergots (n = 4), and butalbital compounds (n = 28). A total of 115 subjects had both a mood and anxiety disorder. Personality disorders were observed in 70 patients.

Overall, 78% of completers had moderate to significant pain reduction. These patients had comparable improvement in mood, function, and behavior.

The authors report that 84% of patients with medication overuse headache attained moderate to significant improvements in headache control, compared to 69% of non-overusers (p <>

"Comparisons involving the presence or absence of a personality disorder diagnosis found that patients with personality disorders were more often opioid-dependent (62.3% versus 37.7%, p <>Source : http://www.medscape.com/viewarticle/703005?src=mpnews&spon=34&uac=133298AG

May 18, 2009 — A protocol including metoclopramide plus diphenhydramine may be helpful for hyperemesis gravidarum (HG), the most severe form of nausea and vomiting during pregnancy, according to the results of a retrospective cohort study reported in the May issue of the European Journal of Obstetrics & Gynecology and Reproductive Biology.

"[HG] is the second most common reason for hospitalisation during pregnancy," write Anaïs Lacasse, BSc, from the University of Montreal in Quebec, Canada, and colleagues. "Since 2002, a new HG treatment protocol consisting of metoclopramide plus diphenhydramine was put in place at CHU Sainte-Justine, affiliated to University of Montreal, Quebec, Canada.

The objectives of this study were to evaluate the effectiveness of this new HG protocol regarding length of hospitalisation for HG, rate of rehospitalisation, evolution of nausea and vomiting symptoms, and rate of adverse events."

From 2002 to 2006, 130 pregnant women diagnosed with HG were treated at CHU Sainte-Justine with the new protocol, consisting of intravenous (IV) metoclopramide 1.2 to 1.8 mg/hour plus diphenhydramine 50 mg every 6 hours. Outcomes in these women were compared with those in a historical control group of 99 women with HG who were treated in the same institution between 1998 and 2001 with IV droperidol 0.5 to 1 mg/hour plus diphenhydramine 25 to 50 mg every 6 hours.

Compared with the old protocol including droperidol, the new protocol was associated with greater improvement in vomiting symptoms (36% vs 21%; P = .0397), with fewer adverse events. Both protocols were associated with similar rates of reduction in nausea symptoms, length of hospitalization (3.7 days vs 3.1 days), and rate of rehospitalisation for HG (19.23% vs 24.44%).

"The new protocol consisting of the combination of metoclopramide and diphenhydramine appears to be a good option in the management of hyperemesis gravidarum," the study authors write. "The combination metoclopramide and diphenhydramine was associated with a higher improvement of vomiting symptoms, and fewer adverse events."

Limitations of this study include that the baseline HG status at first hospitalization was different between the 2 study groups (but the severity of vomiting symptoms on day 1 of the first hospitalization was not different between groups). Other limitations include a lack of data for hematocrit, liver function, blood urea, or creatinine; and a small sample size, limiting conclusions on the safety of metoclopramide plus diphenhydramine during pregnancy.

"The new HG protocol was not better than the droperidol and diphenhydramine combination when looking at improvement of nausea symptoms, length of hospitalisation, and rehospitalisations for HG," the study authors conclude." However, its use is justified given safety concerns regarding the use of droperidol."

Source : http://cme.medscape.com/viewarticle/702960?src=mpnews&spon=34&uac=133298AG

May 6, 2009 — The World Health Organization (WHO) has issued Guidelines on Hand Hygiene in Health Care, offering a thorough review of evidence on hand hygiene in healthcare and specific recommendations to improve hygiene practices and reduce transmission of pathogenic microorganisms to patients and healthcare workers (HCWs).

The guidelines target hospital administrators and public health officials as well as HCWs, and they are designed to be used in any setting in which healthcare is delivered either to a patient or to a specific group, including all settings where healthcare is permanently or occasionally performed, such as home care by birth attendants. Individual adaptation of the recommendations is encouraged, based on local regulations, settings, needs, and resources.

Hand Hygiene Indications

Indications for hand hygiene are as follows:

• Wash hands with soap and water when visibly dirty, when soiled with blood or other body fluids, or after using the toilet.

• Handwashing with soap and water is preferred when exposure to potential spore-forming pathogens, such as Clostridium difficile, is strongly suspected or proven.

• In all other clinical situations, use an alcohol-based handrub as the preferred means for routine hand antisepsis, if hands are not visibly soiled. Wash hands with soap and water if alcohol-based handrub is not available.

• Hand hygiene is needed before and after touching the patient; before touching an invasive device used for patient care, whether gloves are used; after contact with body fluids or excretions, mucous membranes, nonintact skin, or wound dressings; if moving from a contaminated body site to another body site on the same patient; after touching inanimate surfaces and objects in the immediate vicinity; and after removing gloves.

• Hand hygiene is needed before handling medication or preparing food using an alcohol-based handrub or handwashing with water and either plain or antimicrobial soap.

• Soap and alcohol-based handrub should not be used together.

Hand Hygiene Techniques

Specific recommendations for hand hygiene technique are as follows:

• Rub a palmful of alcohol-based handrub over all hand surfaces until dry.

• When washing hands, wet hands with water and apply enough soap to cover all surfaces; rinse hands with water and dry thoroughly with a single-use towel. Whenever possible, use clean, running water. Avoid hot water, which may increase the risk for dermatitis.

• Use the towel to turn off the tap or faucet, and do not reuse the towel.

• Liquid, bar, leaf, or powdered soap is acceptable; bars should be small and placed in racks that allow drainage.

Surgical Hand Preparation

Specific recommendations for surgical hand preparation are as follows:

• Before beginning surgical hand preparation, remove jewelry. Artificial nails are prohibited.

• Sinks should be designed to reduce the risk for splashes.

• Visibly soiled hands should be washed with plain soap before surgical hand preparation, and a nail cleaner should be used to remove debris from underneath the fingernails, preferably under running water.

• Brushes are not recommended.

• Before donning sterile gloves, surgical hand antisepsis should be performed with a suitable antimicrobial soap or alcohol-based handrub, preferably one that ensures sustained activity. Alcohol-based handrub should be used when quality of water is not assured.

• When using an antimicrobial soap, scrub hands and forearms for the length of time recommended by the maker, usually 2 to 5 minutes.

• When using an alcohol-based surgical handrub, follow the maker's instructions; apply to dry hands only; do not combine with alcohol-based products sequentially; use enough product to keep hands and forearms wet throughout surgical hand preparation; and allow hands and forearms to dry thoroughly before donning sterile gloves.

Selecting Hand Hygiene Agents

Some specific recommendations for selection and handling of hand hygiene agents are as follows:

• Provide effective hand hygiene products with low potential to cause irritation.

• Ask for HCW input regarding skin tolerance, feel, and fragrance of any products being considered.

• Determine any known interaction between products used for cleaning hands, skin care products, and gloves used in the institution.

• Provide appropriate, accessible, well-functioning, clean dispensers at the point of care, and do not add soap or alcohol-based formulations to a partially empty dispenser.

Skin Care Recommendations

Some specific recommendations for skin care are as follows:

• Educate HCWs about hand-care practices designed to reduce the risk for irritant contact dermatitis and other skin damage.

• Provide alternative hand hygiene products for HCWs with confirmed allergies to standard products.

• Provide HCWs with hand lotions or creams to reduce the risk for irritant contact dermatitis.

• Use of antimicrobial soap is not recommended when alcohol-based handrub is available. Soap and alcohol-based handrub should not be used together.

Recommendations for Glove Use

Some specific recommendations for use of gloves are as follows:

• Glove use does not replace the need for hand hygiene.

• Gloves are recommended in situations in which contact with blood or other potentially infectious materials is likely.

• Remove gloves after caring for a patient, and do not reuse.

• Change or remove gloves if moving from a contaminated body site to either another body site within the same patient or the environment.

"In hand hygiene promotion programmes for HCWs, focus specifically on factors currently found to have a significant influence on behaviour, and not solely on the type of hand hygiene products," the guidelines authors write. "The strategy should be multifaceted and multimodal and include education and senior executive support for implementation. Educate HCWs about the type of patient-care activities that can result in hand contamination and about the advantages and disadvantages of various methods used to clean their hands."

Four of the guidelines authors have disclosed various financial relationships with GOJO, Clorox, and GlaxoSmithKline, and other companies and institutions. A complete description of their disclosures is available in the original article. The other guidelines authors have disclosed no relevant financial relationships.

WHO Guidelines on Hand Hygiene in Health Care. May 2009.

Clinical Context

Study Highlights

• Indications for washing hands with soap and water include visibly dirty hands, hands visibly soiled with body fluids, or after using the toilet.
• Handwashing with soap and water is preferred after exposure to potential spore-forming pathogens, including Clostridium difficile outbreaks.
• Alcohol-based handrub is preferred in the following situations if hands are not visibly soiled: before and after touching a patient; before handling an invasive device for patient care; after contact with body fluids or excretions, mucous membranes, nonintact skin, or wound dressings; between contact with a contaminated body site to another site on the same patient; after contact with inanimate surfaces and objects; and after removing sterile or nonsterile gloves.
• Handwashing with soap and water is recommended when alcohol-based handrub is unavailable.
• Alcohol-based handrub or soap and water can be used before handling medication or preparing food.
• Concomitant alcohol-based handrub and soap use is not recommended.
• Soap and water hand-washing technique includes using a towel to turn off the faucet, thorough drying of hands, and single towel use.
• Acceptable forms of soap are liquid, bar, leaf, or powdered.
• Bar soap racks should allow drainage to ensure that the soap dries.
• Alcohol-based handrub technique includes applying palmful amount of handrub, covering all surfaces, and rubbing hands until dry.
• Surgical hand hygiene recommendations include removal of jewelry, no brushes, and use of either antimicrobial soap or alcohol-based handrub according to the maker's recommendations.
• Selection of hand hygiene agents should consider input from HCWs, interaction with other products or gloves, risk for contamination, accessibility and proper functioning of dispensers, approval of dispensers for flammable materials, and cost comparisons.
• Soap or alcohol-based handrub should not be added to partially empty soap dispensers.
• Skin care irritation in HCWs can be avoided by providing educational programs, alternative hand hygiene products for those with allergies or adverse reactions to standard products, and hand moisturizers to reduce irritant contact dermatitis.
• Glove use does not replace the need for handrub or handwashing.
• Gloves should be used if contact with potentially infectious body fluids, mucous membranes, or nonintact skin is anticipated.
• Gloves should be removed or changed after each patient or after contact with a contaminated body site.
• Artificial nails or extenders should not be used, and the length of natural nail tips should be less than 0.5 cm.
• Educational and motivational programs for HCWs should focus on behavior; be multimodal; include senior executive support; educate about the advantages and disadvantages of various hand hygiene methods; monitor adherence and provide performance feedback; and encourage partnership between patients, families, and HCWs.
• Healthcare administrators should provide and monitor safe, continuous water supply; provide alcohol-based handrub at the point of patient care; prioritize compliance; provide leadership, administrative support, and financial resources; ensure training; implement a multidisciplinary, multifaceted, and multimodal program to improve adherence; and adhere to national safety guidelines and local legal requirements.
• National governments should prioritize adherence; consider funded, coordinated implementation and monitoring; support strengthening of infection control in healthcare settings; promote community hand hygiene; and encourage use of hand hygiene as a quality indicator in healthcare settings.

Clinical Implications

• The WHO guidelines recommend handwashing with soap and water for visibly dirty hands, hands visibly soiled with body fluids, after toilet use, exposure to potential spore-forming pathogens, and if alcohol-based handrub is not available in other situations.
• The WHO guidelines recommend alcohol-based handrub before and after touching patients; before handling invasive devices; after contact with body fluids or excretions, mucous membranes, nonintact skin, or wound dressings; between touching contaminated body site and another body site; after contact with inanimate surfaces and objects; and after removing gloves.

Source : http://cme.medscape.com/viewarticle/702403?src=cmenews

Children with attention-deficit/hyperactivity disorder (ADHD) have alterations in the development of parts of the cortico-striato-thalamo-cortical network, according to a report in the December Archives of General Psychiatry.

"This study suggests that earlier developing brain areas, such as subcortical areas (which controls motoric behavior), may influence the development of later developing brain areas, such as the prefrontal cortex (which plays a major role in executive functions)," Dr. Jeffrey A. Stanley from Wayne State University School of Medicine, Detroit, told Reuters Health.

Dr. Stanley and colleagues used phosphorus 31 spectroscopy methods to investigate alterations in membrane phospholipid precursor levels in the basal ganglia and prefrontal cortex of 31 children with ADHD and 36 healthy comparison subjects.

"In vivo 31P spectroscopy is a sensitive tool in assessing cortical development, an approach that may be more sensitive than anatomical MRI studies," Dr. Stanley explained. "In vivo 31P spectroscopy has the potential of assessing these developmental changes over time."

Compared with healthy controls, children with ADHD had significantly lower bilateral membrane phospholipids precursor levels in the basal ganglia and higher membrane phospholipid precursor levels in the inferior parietal region (particularly on the right side), the authors report.

These changes were most notable in older children with ADHD when compared with their healthy counterparts, the researchers note.

"These findings, which corrected for the proportion of gray matter tissue volume within the 31P spectroscopy voxels in the analyses, are consistent with MRI studies noting structural changes in these regions," the investigators say.

Dr. Stanley hopes to conduct "a large longitudinal study" to investigate the biochemical changes in children and adolescents with ADHD compared with those in healthy children.

"We hope to be more accurate in identifying when and where in the brain these developmental deviations occur, which would position us well to address whether treatment regimens can in fact reverse the course of illness (e.g., using cognitive behavioral therapy along with psychostimulants)," Dr. Stanley said.

Source : http://www.medscape.com/viewarticle/585507

May 20, 2009 (San Francisco, California) — If performed under carefully controlled conditions, playing video games may help improve concentration in children with attention-deficit/hyperactivity disorder (ADHD), according to a small study presented here at the American Psychiatric Association (APA) 162nd Annual Meeting.

In the study of 10 patients, playing the video game Gran Turismo, an automobile-racing game, increased electroencephalograph (EEG)-measured beta waves, which are often associated with concentration. Parents and teachers of the children also indicated improvements in behavior after 10 regular sessions of video games.

"We wanted to supply an alternative way to treat children, rather than just using stimulants,” Bhupendra Gupta, MD, from Sullivan University, in Louisville, Kentucky, told Medscape Psychiatry. "As well as documenting improved concentration with EEG, we also found that the children showed substantial improvements in behaviors at school and home and were more compliant with their medications," he added.

The children were treated for 10 to 15 sessions every 2 weeks for 6 months, according to Dr. Gupta. During the video gaming sessions, the children wore a virtual helmet that held EEG sensors. EEG data were plotted and quantified for 15 minutes per session and analyzed statistically. Results showed that theta waves decreased and beta waves increased during the gaming sessions.

Compliance Also Improved

At baseline and after 10 sessions, parents and teachers of the children also completed the Connors Behavior Rating Scale. At baseline, the children scored a mean of 26.2, but after 10 sessions of video games, the children's scores decreased to a mean of 9.2. Parents indicated there were significant improvements in homework habits as well as school grades.

"These studies suggest that video games can have implications in improving ADHD in children and adults," the researchers concluded. "Video games can be an effective method for behavior modification in children with ADHD. This method can [also] provide a noninvasive method of improving concentration in the workplace for pilots and troops."

Dr. Gupta noted that playing video games motivated the children with ADHD to come for treatment, and their compliance with their medication regimens thus improved.

"Having ADHD is a stigma for kids, and so the concept was to make treatment fun for them — not to make them feel they have to go to a physician to get medication or an injection," he said.

Interpret with Caution

However, experts at the meeting noted that the results of the study should be interpreted with caution. One reason is the study's small sample size. Another problem is that video gaming is known to lead to addiction. "It can be like any other behavioral addiction or obsessive activity," said Michael Brody, MD, a fellow of the APA and the author of the book Messages: Self Help Through Popular Culture.

"Yet if it helps kids focus and is done in a balanced way — for instance, once a week for an hour or several hours — that's fine,” Dr. Brody added. “Unfortunately, video games are often violent, and they can lead children to addiction. Children playing these games may not pay attention to anything else."

"You can't really make a blanket statement that video games will improve concentration," he said. "But any activity that gets people off the couch — as long as it's balanced — can be a good idea."

Source : http://www.medscape.com/viewarticle/703152?sssdmh=dm1.474949&src=nldne

The US government's tentative plan to develop a stand-alone vaccine for the swine-origin H1N1 influenza virus could strain the nation's vaccine makers to the point of reducing production of seasonal flu vaccine this fall, an official with the National Institutes for Health told Medscape Infectious Diseases.

It's all a matter of striking a balance between the unknown threat of the H1N1 influenza virus and the known threat of the seasonal flu virus, said Gary Nabel, MD, director of the vaccine research center at the National Institute of Allergy and Infectious Diseases.

"There may have to be compromises," said Dr. Nabel. "We'll know more as time goes on."

Balancing the supply of 2 different vaccines is just one challenge facing public health officials as they contemplate vaccinating Americans against a new flu virus that has resulted in 141 confirmed cases and 1 death in the United States, killed possibly 170 people in Mexico, and emerged in at least 9 other nations. Questions remain for public health officials about whether citizens will go to the trouble of getting both seasonal and H1N1 vaccines and how to reduce potential arguments over who in the general public should be the first to receive vaccination with the limited supplies of H1N1 vaccine in the fall.

Yesterday, Richard Besser, MD, acting director of the Centers for Disease Control and Prevention (CDC), said that the CDC is discussing a plan to manufacture a separate H1N1 vaccine — if it's needed — after completing the production of next fall's seasonal flu vaccine, which is now under way. The alternative, considered unrealistic, would be to delay production of the seasonal vaccine so that the H1N1 vaccine could be incorporated into it.

Vaccine makers would create a 2-dose regimen for the H1N1 vaccine — a primer dose at first, followed by second to "seal the deal," said Christine Layton, PhD, MPH, a public health researcher and influenza pandemic expert at RTI International in Research Triangle Park, North Carolina. To immunize roughly 300 million Americans, therefore, the federal government would need 600 million doses. That's 4 times the number of doses of seasonal flu vaccine that vaccine makers were projected to make for the 2008–2009 flu season, according to the CDC. "Production will be a big challenge," said Dr. Layton.

Can the United States successfully conduct a 2-front war on flu viruses? On the bright side, experts say that our vaccine-making capacity is stronger than ever. During the 2004–2005 flu season, a single company, Sanofi Aventis, was putting injectable seasonal flu vaccines into the immunization pipeline. In 2009, 6 companies are licensed to manufacture seasonal flu vaccines in this country (one of them makes a nasal spray), and all of them are working to expand their production capacity, according to the CDC.

There are other positives. Dr. Nabel said the recipe for this fall's seasonal flu vaccine will contain 2 of the 3 influenza virus strains used in the vaccine for the 2008–2009 flu season, making it easier to produce. That good fortune could help vaccine makers maintain adequate supplies of seasonal flu vaccine while pumping out an H1N1 version, he said.

Manufacturers also can stretch their supply of H1N1 vaccine by adding so-called adjuvants, which amplify the immune response. Growing vaccine-bound viruses in cell cultures as opposed to chicken eggs — the traditional and more cumbersome process — also promises to boost production, but not necessarily in 2009, added Dr. Nabel. "I doubt that it could satisfy the demand that is out there."

All in all, said Dr. Nabel, the production equation depends on how severe the H1N1 virus outbreak turns out to be. To create enough H1N1 vaccine, it may be necessary to cut back on seasonal vaccine production, he said. That prospect troubles experts such as Dr. Layton, since seasonal influenza claims the lives of 36,000 people each year. "It's not an inconsequential disease," she said.

However, stinting on the supply of an H1N1 vaccine creates problems, too. As it is, the federal government envisions having 50 to 80 million doses of the H1N1 vaccine this fall, with the rest of the necessary doses becoming available later in the year as manufacturing continues.

"Early on, when the vaccine is in short supply, the biggest challenge will be determining how it will be administered in a way that's epidemiologically appropriate and ethically sound," said Dr. Layton. Faced with limited quantities, she said, the general public may fight over the vaccine just as shoppers sometimes fight over store merchandise on sale. "It's an unfortunate part of human nature," she said.

To be sure, the US Department of Health and Human Services probably will recommend a pecking order for who should receive any H1N1 vaccine, said Dr. Nabel. HHS took that same approach in gearing up for a possible avian flu pandemic 3 years ago, putting the vaccine and antiviral manufacturing workforce at the top of the list, followed by various types of healthcare workers, and then groups of vulnerable patients such as persons older than 65 years with 1 or more influenza high-risk conditions (not including essential hypertension) and pregnant women.

However, such priority recommendations are subject to debate. While healthy persons aged 6 to 64 years are on the bottom of the list for an avian flu vaccine, some have argued that healthy children should be closer to the top during a pandemic, said Dr. Layton. "Elderly persons — particularly those who are ill — often have minimal immune response to vaccines," she said. "Young children, although potentially healthier than sick elderly persons, are more likely to have a robust immune response to immunization and pose a greater risk of spreading infection. [They] often are infectious for greater time periods than adults and come in contact with more people. As such, there are those who assert that young children are a more reasonable group to receive vaccines than frail elderly," she said.

In addition to competing for production resources, separate seasonal and H1N1 vaccines also may confuse patients. "It will be a challenge for public health officials to explain to people what vaccines they're getting, and what they're good for," Dr. Layton added.

The production and administration problems created by separate vaccines for the seasonal and H1N1 influenza will disappear if public health authorities decide to incorporate an H1N1 vaccine into the seasonal vaccine for the fall of 2010. They would have plenty of time to determine whether they should substitute the H1N1 virus for 1 of the 3 viruses used in the seasonal vaccine design, or whether they should make it a fourth component.

Then again, that's assuming the H1N1 virus becomes the major health threat that people fear. As of now, the federal government is on course to produce a H1N1 vaccine, but it could later nix the idea of mass production if the new virus fizzles out. Making the right decision will be tricky, said Gigi Kwik Gronvall, PhD, a senior associate and immunologist by training at the Center for Biosecurity at the University of Pittsburgh Medical Center in Pennsylvania.

"You don't know what the swine flu will do," said Dr. Gronvall. "Biology is always full of surprises. The data changes from day to day, so you need to keep an eye on what's going on and avoid both overreacting and underreacting. And you don't want politics to influence these decisions."

Source : http://www.medscape.com/viewarticle/702229

When President Obama remarked in his April 29 press conference that closing the US-Mexico border to prevent the spread of swine flu was akin to closing the barn door after the horses had bolted, he was reflecting the opinion of many public health experts.

"Given the widespread presence of the virus across many countries containment is probably not feasible, and efforts need to focus increasingly on mitigation," writes Richard Coker, MBBS, MSc, from the London School of Hygiene and Tropical Medicine's Faculty of Tropical Medicine, at the University of Mahidol, Bankgok, Thailand, in an editorial published online April 30 in the BMJ.

As of April 30 at 11:00 am ET, the CDC listed a total of 141 confirmed cases of the swine influenza A H1N1 strain, with cases in Arizona (4), California (13), Colorado (2), Delaware (4), Illinois (3), Indiana (3) Kansas (2), Kentucky (1), Massachusetts (2), Michigan (2), Minnesota (1), Nebraska (1), Nevada (1), New Jersey (5), New York (50), Ohio (1), South Carolina (16), Texas (28), and Virginia (2).There was also 1 reported death, a child from Mexico visiting relatives in Texas.

The World Health Organization (WHO) said that as of 6:00 am GMT, May 1, a total of 331 cases had been reported from 11 countries, in addition to the United States and Mexico, including Austria, Canada, Germany, Israel, the Netherlands, New Zealand, Spain, Switzerland, and the United Kingdom. The WHO has raised its level of alert to 5 on a scale of 6, indicating that a global pandemic is imminent.

Plans Are One Thing, Implementation Another

Although most industrialized and many developing nations have learned the lessons of the severe acute respiratory distress syndrome (SARS) and avian influenza H5N1 strain epidemics, and have both pandemic contingency plans and stockpiles of antiviral medications in place, developing countries may still be unequipped to contain or treat outbreaks, according to the BMJ editorial and a similar one published online April 28 in The Lancet.

"Analyses of national strategic plans around the world show that although most countries now have plans, many countries, especially developing countries, will struggle to put them into operation," Dr. Coker writes. "This is because they have limited health system resources to call on in the event of a pandemic; they have not stockpiled antiviral drugs in anything like the numbers needed for mitigation purposes (and if they had, they might struggle to mobilize them effectively); and they are unlikely to receive an effective vaccine early (if at all), once it is produced in large amounts."

That concern is echoed by the editors of The Lancet, who write in an editorial that "of particular concern is the ability of low-income and middle-income countries to detect and mitigate the effects of this new virus on their populations. History has shown that developing countries are disproportionately affected by an influenza pandemic."

Unreported Cases

Dr. Coker notes that nearly all of the confirmed cases of influenza A H1N1 — the term now used by the CDC and the WHO to avoid casting aspersions on swine and the pork products industry — are in industrialized countries with good surveillance systems. It raises the question, he says, of whether there aren't more, unreported cases lurking in the background, unreported to public health systems in developing countries.

And it isn't just in less affluent places: New York City Mayor Michael Bloomberg said at a press conference on April 30 that in addition to the laboratory-confirmed cases, there were many more likely cases among students at the St. Francis Preparatory School, where the outbreak first surfaced in the city.

"If we went and tested all of the students at St. Francis, we'd have hundreds of cases. We know what they've got and we'd just be tying up resources," Mr. Bloomberg said.

According to Dr. Coker, developing countries have nowhere near the amount of the antiviral agents oseltamavir (Tamiflu, Roche) or zanamavir (Relenza, GlaxoSmithKline) needed for mitigation efforts, and even if they did, would be hard-pressed to distribute them.

"[A]though many developed countries, including most of Western Europe and the US, have sizeable stockpiles of antiviral drugs, most low and middle income countries have low or non-existent stocks," he writes. "The rapid response stockpile of three million treatments of oseltamivir, and the two million treatments stockpiled by WHO as regional stockpiles for use in developing countries, are intended principally for rapid containment, and they will not go far to support mitigation efforts."

In addition, he cites several studies suggesting that should an effective vaccine become available, developing countries would be unlikely to get it in time or indeed at all.

In an interview with Medscape Infectious Diseases, Georges C. Benjamin, MD, FACP, FACEP (E), executive director of the American Public Health Association, said that public health authorities around the world will need to cooperate to ensure that developing nations have the resources they need in the event of a global pandemic.

"We need to be looking at prepositioning medicine and supplies on a global basis, to be able to aid those countries," he said. "We know what happens when they have drought, we know what happens when they have severe infectious diseases, and now we have to make sure that they have access to clean water, that they have surveillance systems in place for early detection when disease hit those communities, and understand that they may not have clean water available or soap for handwashing in small villages.

"Those are always real challenges," Dr. Benjamin said. "We need to figure out how to empower the leaders in those countries to get the message out, and we ought to be doing that now."

Swine + Avian Influenza = ?

Another issue that Dr. Coker and others have raised is that a new strain of flu could arise from the potential intermingling of swine and avian flu strains.

"Immunity to H1N1 will not offer protection to H5N1 if that also becomes readily transmissible between humans," Dr. Coker writes. "As H1N1 spreads to areas where H5N1 is endemic, do we face an even greater challenge — that of reassortment of these two viruses and the threat of another pandemic?"

In an interview with Medscape Infectious Diseases earlier this week, Neal A. Halsey, MD, professor in the Department of International Health, Bloomberg School of Public Health, Johns Hopkins University in Baltimore, Maryland, notes that swine "are a great mixing bowl, because they are susceptible not only to the swine flu, but also influenza from birds and influenza from humans."

An individual pig can contain several different viruses simultaneously, Dr. Halsey said, and these viruses can mix into new and potentially highly infectious forms.

Dr. Benjamin added that other conditions in developing countries may conspire to exacerbate pandemic influenza when it arrives.

"Two things we have not yet seen: (1) we know that even a mild pandemic that results in people getting severely dehydrated, especially in children, with fever and not enough water to drink can be life-threatening, and (2) is the effect on a population which is heavily impacted by HIV/AIDS or has another automimmue problem. We've not seen that yet, but it's only a matter of time," he said.

Asked whether, given the global economic crisis, public health authorities would be able to coordinate funds and efforts, Dr. Benjamin had a stark and simple answer: "We don't have a choice."

Source : http://www.medscape.com/viewarticle/702227

May 20, 2009 (San Diego, California) — In a special panel session here at ATS 2009: the American Thoracic Society International Conference, experts and public-health officials discussed the current situation and ways hospitals can prepare for a potential second wave of infections in the fall.

The novel influenza A (H1N1) virus "sneaked in the door while health authorities who should have known better were busy closing windows," said Carol J. Cardona, DVM, PhD, ACPV, from the Department of Population Health and Reproduction, and professor in the School of Veterinary Medicine, University of California, Davis, to an overflow crowd of thoracic and critical-care physicians.

"This virus has followed the pattern of all historic pandemics, and we've missed some precursors out there and we've missed some signals," Dr. Cardona said. She is a virologist and an expert in determining how disease-causing agents damage their hosts. Dr. Cardona's segment of the presentation was entitled "Swine Flu: Molecular Clues to the Origin, Transmission, and Pathogenesis of the Virus."

Failure to Detect Precursors

Dr. Cardona said she anticipates mutations in the virus. "Expect to see stepwise changes over time and incremental changes over time in influenza A viruses." She pointed out that there is opportunity for reassortment between and among viruses that will result in the generation of new antigenically novel strains filtered through poultry and pigs to humans. "You have several segments from one, then another, and then a third, for a triple reassortment; this results in big leaps in the genome," she said, referring to the origins of H1N1.

"We're providing ample opportunity with animals being raised quickly in large groups, where you have many, many generations. It's an efficient way to raise food and an effective way to spread viruses," Dr. Cardona said. "It is the replicative properties of influenza virus hemagglutinin [HA] subtype diversity mutants with altered receptor-binding properties that underlie virulence and spread. The viruses come together and reassert into pathogens that can infect humans. The disease outcomes are influenced by host immunity; viruses with novel HAs can evade host immunity and cause these diseases."

Dr. Cardona explained that there are no antibodies to H1N1 influenza, which is why it has spread so rapidly. "And that's the unusual thing about this virus: we failed to detect precursors and we failed to find it in swine." She said that the H1N1 influenza has the ability to spread quickly. "It could happen within a few days, the mutation in animals, and infect other species," she said, pointing out the recent swine herd in Canada where, earlier this month, a traveler carried the new H1N1 virus from Mexico to Canada, infecting his family along with a herd of swine, according to Canadian health officials.

Also on the panel was Rear Admiral Kenneth G. Castro, MD, acting chief/science officer of the Centers for Disease Control and Prevention Emergency Operation Center, who told attendees that because this H1N1 influenza is spread from person to person, it's beginning to prepare for a pandemic. "This is what we are preparing for and worrying about," he said. The title of his presentation was "Human Cases in the United States of Swine Influenza."

He predicted that we have not seen the last of this H1N1 influenza: "Clearly, this virus has readily spread across the [United States] at a time we're no longer experiencing influenza. The criteria for this virus have nothing to do with the severity problem in pandemic planning. This is very likely to be circulating and you can expect to see it again when our virus season occurs."

Dr. Castro pegged the number of confirmed or probable cases in the United States at 5469, with 6 deaths (as of May 20, 7 deaths; a 44 year-old man in St. Louis who had visited Mexico died) in 48 states and the District of Columbia. Only Wyoming and West Virginia have had no confirmed cases. The median age is 17 years (range, 1 month - 87 years); 63% of those afflicted had an underlying medical condition at the time of illness onset. The average stay in a hospital is 4 days, with a median stay of 5 days (range, 2 - 31 days); 24% were admitted to the hospital's intensive care unit (ICU).

He described the clinical presenting characteristics as fever, cough, shortness of breath, and sore throat, with 52% of presentations having abnormal findings of bilateral infiltrates consistent with pneumonia; 31% also had asthma or diabetes. Of the population presenting to hospitals, 66% were treated with antivirals and 85% were treated with 1 to 7 antibiotics (overlapping), with a median of 3. "Everything has been thrown into the equation to try to treat these hospitalized patients," Dr. Castro said.

He recommended that patients with any early signs of influenza stay home, and he pointed out that closing schools was no guarantee that students wouldn't assemble at local malls.

Second Wave Likely

Also on the panel was Christian E. Sandrock, MD, MPH, deputy health officer of Yolo County in Sacramento, California, and assistant clinical professor, Division of Pulmonary and Critical Care Medicine, University of California, Davis, School of Medicine. He told the audience: "With regard to what may happen in the Southern Hemisphere in the next few months, I get to be intensely prophetic or the village fool." His presentation was entitled "H1N1 2009: Should We Be Concerned About a Second 'Wave'?"

He compared previous worldwide pandemic patterns that occurred in the twentieth century — the 1918, 1957, 1968/1969, and 1977 (in children) pandemics that represented 3 different antigenic subtypes of the influenza A virus (H1N1, H2N2, and H2N2) — to this current swine-origin influenza A (H1N1) virus first detected in April 2009.

"The 1 difference in pattern is that this current virus is widespread, around the world to multiple continents, and we're heading toward a second wave. We're moving in that direction," he said, "and the second wave is very likely."

Dr. Sandrock said there is no vaccine that will protect against the virus, but he said that if populations are old enough to have experienced the 1968 strain, for instance, they may have a host-adapted MHC I primed T-cell response with epitopes, [which] is appropriate for viral clearance [and] may confer some protection and result in a mild to moderate disease, where the host would just "feel crummy." Dr. Sandrock added that patients who present with asthma and a fever should not be written off but should be screened for influenza.

When asked how quickly he thought the current virus would mutate, he called that the "million-dollar question." Dr. Sandrock noted that "it takes a while for the virus to mutate and spread, but once it's up and going, we'll see a surge in the numbers and deaths."

Lewis Rubinson, MD, PhD, assistant professor of medicine, pulmonary and critical care medicine, Harborview Medical Center in Seattle, Washington, gave a segment entitled, "Swine Flu: What if the Critical Care Need Increases?" He said that the goals of the ICU in this era of phase 5 are to keep the hospital staff safe. "One of the hardest things for providers is how to integrate into the hospital but not take it over; there's nothing worse than having a leader working alone."

(The World Health Organization [WHO] raised the worldwide pandemic alert level to phase 5 on April 29; phase 5 is a "strong signal that a pandemic is imminent"; however, there is a current debate at the WHO World Health Assembly in Geneva, Switzerland, as to whether the WHO should raise the alert level to phase 6, which would indicate that a pandemic is under way. US Secretary of Health and Human Services Kathleen Sebelius said in Geneva that the United States is already taking phase 6 measures.)

Risk Stratification and Prophylaxis

Dr. Rubinson warned that triaging could get very confusing if coordination and integration within the rest of the institution are not on board. "When you have groups operating independently, you can lose control of the system," he said. "You don't have convalescent homes evacuating patients to emergency rooms." Dr. Rubinson said that hospitals needed to have standardized decision-making in place. "Maybe we should start thinking about risk stratification and prophylaxis at this point in time — the key interventions should take place in cases where patients might not survive if we do not provide them."

He suggested that hospitals start looking around at items most frequently used in their ICUs and get stocked up now. "Even if you're a behemoth, you will be competing with all the other behemoths for supplies, and if you run out of something like corticosteroids or ventilator circuits, you're in trouble." Dr. Rubinson noted that even if this virus "fizzles out," stockpiled supplies will eventually be used.

He said it might get to the point that entire hospitals will be converted to ICU care, because institutions cannot care for ill patients in tents that are not equipped with liquid oxygen systems. He suggested that acute respiratory distress syndrome and asthma would be the predominant conditions of presenting patients. "Despite excellent care, people are still dying and until recently there were no good data to predict just how sick people would be; these are sick people who will require a full-court press of what we can provide."

Rounding out the group was Guillermo Dominguez-Cherit, MD, who heads up the ICU in the Department of Critical Care Medicine, Instituto Nacional de Ciencias Medicas y Nutrición in Mexico City, Mexico, whose presentation was entitled "Caring for Critically Ill Patients in Mexico City Infected with Swine Flu." He informed attendees that as of May 4, 2009, there were a total of 3646 cases, with 70 deaths as of May 18, 2009. He described life in Mexico since April 17, when the Minister of Health closed schools and took other extreme measures. He showed slides of empty streets and business centers. "You can imagine the impact on the economy," he said.

Staffing in Mexico's hospitals had been an issue, with some employees refusing to come to work, final-year nursing students were being used to staff ICUs, and they were recruiting physicians from other departments, such as anesthesia and surgery, to help care for the influenza patients, Dr. Dominguez-Cherit said.

He added that at least half of all hospitalized patients had 2 or more comorbidities, and 78% had bilateral infiltrates on presentation. Other symptoms were respiratory distress, fever (100%), diarrhea, conjunctivitis, vomiting, coryza, weakness, and myalgias. The time from the first symptom to admittance to a medical facility was 6 days, and once in the hospital, the time to ICU admittance was 1.6 days, with an average hospital stay of 9.5 days. The locations of deaths within medical facilities were the ICU and the emergency department.

Dr. Dominguez-Cherit suggested that a global plan be in place so that action could be quickly taken to combat the anticipated influx of disease.

Source : http://www.medscape.com/viewarticle/703113?sssdmh=dm1.474949&src=nldne

May 20, 2009 (Ibaraki, Japan) — A higher level of cardiorespiratory fitness is associated with a lower risk of all-cause mortality, coronary heart disease (CHD) and cardiovascular disease (CVD) events, according to a meta-analysis of 33 trials comprising more than 187 000 healthy men and women published in the May 20, 2009 issue of the Journal of the American Medical Association [1].

Dr Satoru Kodama (University of Tsukuba Institute of Clinical Medicine, Ibaraki, Japan) and colleagues found that participants with the lowest level of cardiorespiratory fitness had a 70% higher risk for all-cause mortality and a 56% higher risk for CHD/CVD events compared with participants with the highest level of cardiorespiratory fitness. Participants with intermediate levels of cardiorespiratory fitness had a 40% higher risk for all-cause mortality and a 47% higher risk for CHD/CVD events than participants with the highest cardiorespiratory fitness.

Because the study showed cardiorespiratory fitness to be such a strong predictor of mortality and CVD/CHD risk, Kodama and colleagues suggest that it be made a part of routine CVD/CHD risk assessment. "It is possible that prediction of CHD risk could be improved by including cardiorespiratory fitness with already established risk factors for CHD," they write.

Physical fitness experts concur. "Organizations such as the National Institutes of Health and the American Heart Association should convene consensus panels to make recommendations for including cardiorespiratory fitness in risk-prediction equations," Dr Steven N Blair (University of South Carolina, Columbia) told heartwire in email correspondence.

Survival of the Fittest

Cardiorespiratory fitness is assessed by exercise tolerance testing, but it is rare for clinicians to consider cardiorespiratory fitness when evaluating future risk of CHD, write Kodama et al. "A major reason for lack of consideration of cardiorespiratory fitness as a marker of CHD risk may be that the quantitative association of cardiorespiratory fitness for cardiovascular risk is not well established," they write. "The degree of risk reduction associated with each incremental higher level of cardiorespiratory fitness, the criteria for low cardiorespiratory fitness, and the magnitude of risk associated with low cardiorespiratory fitness have been inconsistent among studies."

They systematically reviewed observational cohort studies using MEDLINE (1966 to December 31, 2008) and EMBASE (1980 to December 31, 2008) and selected studies reporting associations of baseline cardiorespiratory fitness with CHD events, CVD events, or all-cause mortality in men and women. Data were obtained on all-cause mortality for 102 980 participants and 6910 cases and on CHD/CVD for 84 323 participants and 4485 cases.

Cardiorespiratory fitness was estimated as maximal aerobic capacity (MAC) expressed in metabolic equivalent (MET) units, with one MET corresponding to 3.5 mL/min/kg of oxygen consumption. Participants were categorized as low cardiorespiratory fitness (<7.9>>10.9 METs), and risk ratios (RRs) for a 1-MET-higher level of MAC (corresponding to a 1-km/h-higher running/jogging speed) and for participants with lower vs higher cardiorespiratory fitness were calculated with a random-effects model.

Pooled Risk Ratios Per 1-MET-Higher Level of MAC

Outcome	RR	95% CI
All-cause mortality	0.87	0.84–0.90
CHD/CVD events	0.85	0.82–0.88

Risk Ratios for Low Cardiorespiratory Fitness Compared With High, Intermediate Cardiorespiratory Fitness

	RR	95% CI	p
Compared with high cardiorespiratory fitness
All-cause mortality	1.70	1.51–1.92	<0.001
CHD/CVD events	1.56	1.39–1.75	<0.001
Compared with intermediate cardiorespiratory fitness
All-cause mortality	1.40	1.32–1.48	<0.001
CHD/CVD events	1.47	1.35–1.61	<0.001

"These analyses suggest that a minimal cardiorespiratory fitness of 7.9 METs may be important for significant prevention of all-cause mortality and CHD/CVD," the study authors write. The results also indicate that the minimum cardiorespiratory-fitness level that is associated with significantly lower event rates is 9 METs for men at age 40, 8 METs for men at age 50, and 7 METs for men at age 60. For women, it is 7 METs at age 40, 6 METs at age 50, and 5 METs at age 60.

"If the cardiorespiratory-fitness level is expressed in terms of walking speed, men around 50 years of age must be capable of continuous walking at a speed of 4 mph and women must continuously walk at 3 mph for prevention of CHD," Kodama et al write.

Include Cardiorespiratory Fitness as a Risk Factor for CVD

The authors conclude "We suggest that cardiorespiratory fitness, which can be readily assessed by an exercise stress test, could be useful for prediction of CHD/CVD and all-cause mortality risk in a primary-care medical practice."

Blair agreed. He told heartwire , "The literature review was thorough, and the meta-analysis was well done. I agree with the authors that the evidence shows that cardiorespiratory fitness has a very strong inverse association with all-cause mortality and CHD/CVD. This strong and independent association is important, and I also agree with the authors that general risk-prediction equations certainly should include cardiorespiratory fitness. I think it is a major mistake to continue to exclude cardiorespiratory fitness in risk stratification of patients."

Weighing in with his comments on the study, Dr Philip Ades (University of Vermont [UVM] Medical College, Burlington) said that many studies have shown that exercise capacity predicts overall mortality and rate of future cardiac events. "So the general concept is not new," he told heartwire in an interview. "What is noteworthy about this study, however, are the very large numbers, which give it considerable statistical power, and the rigor of the meta-analysis, which was very well done. This study affirms, with a lot of statistical clout, the close relationship between fitness and important medical outcomes such as death and coronary disease."

Ades, who heads the cardiovascular rehab unit at UVM, agrees that clinicians should use cardiorespiratory fitness as a predictor of risk but says that doing a stress test on everyone above the age of 40 or 50 is not feasible.

Stress testing can open a can of worms, he said in an interview. "This is a very complicated question. There can be false positives and false negatives, and the false positives can lead to more expensive tests. It is not cost-effective."

A much better alternative would be to use fitness testing selectively and spend increasingly limited healthcare dollars on a campaign to get people to adopt a healthy lifestyle, Ades said. "Over 65% of Americans are overweight, more than 50% don't exercise, and 20% smoke. So do we want to spend our money on stress tests, or do we want to spend our money on public policy that would encourage people to walk, eat well, stay thin, and not smoke? To me it's a no-brainer. That action should trump prediction."

Source : http://www.medscape.com/viewarticle/703125?sssdmh=dm1.474949&src=nldne

The ongoing insult of environmental tobacco smoke (ETS) in the home during childhood years can contribute to lower lung function and early emphysema later in life due to mechanical stress to the alveolar wall, even in nonsmokers, according to newly analyzed data from the Multi-Ethnic Study of Arthrosclerosis (MESA) released here at ATS 2009: the American Thoracic Society International Conference.

Smoking leads to emphysema in the upper lobes of the lungs; however, panacinar emphysema involves the complete respiratory lobule and is associated with alpha 1-antitrypsin deficiency. Typically, it develops in patients who have never smoked. To date, other risk factors are unknown.

Dr. Gina Lovasi

"We found a statistically significant difference in subjects who lived in a home with regular smokers and we were somewhat surprised to see a difference that was not due to chance," lead investigator Gina S. Lovasi, PhD, MPH, from the Robert Wood Johnson Foundation Health & Society Scholars program, Institute for Social and Economic Research, Columbia University, in New York City, said during a news conference.

The MESA Lung study (an ancillary study of MESA, which is assessing the role of endothelial dysfunction and genetic susceptibility in subclinical chronic obstructive pulmonary disease) used data and computed tomography scan results, piggybacked from coronary artery scans, from the American multiethnic, multisite MESA cohort study of 1781 nonsmoking cardiovascular disease-free healthy adults, aged 45 to 84 years (mean age, 61 ± 10 years), 65% of whom were female, recruited in 2000 to 2002; follow-up is ongoing. Participants reported having smoked fewer than 100 cigarettes, cigars, or pipes of tobacco in their lifetimes; urinary cotinine levels were less than 100 ng/mL.

Childhood ETS exposure was assessed retrospectively as a report of living with people who smoked regularly in the home. The MESA Lung study used a fractal, structural measure of early emphysema and a standard quantitative measure from the cardiac scans to assess the total volume of air-like space in the lungs and the larger clusters of air-like areas in the lungs.

Subjects who lived their childhood in homes with 2 or more smokers, compared with those who lived with no smokers, had a mean alpha that was 0.04 lower and a mean percent emphysema that was 2.1 (P = .03 and 0.01, respectively) higher after adjustment for age, height, education, demographics, history of residing in air-polluted areas, occupational exposure to irritants, and adult ETS. The mean proportion of air-like space in the lungs was 17% for nonsmokers with no childhood ETS, 18% for nonsmokers who lived with 1 smoker as a child, and 20% for those who lived with 2 or more smokers as a child. Childhood ETS was not associated with lung function in this healthy population, the study reported.

"The difference between the highest and the lowest groups was 3%, but we attenuated that to 2% after statistically accounting for other factors and characteristics," said Dr. Lovasi.

Dr. Phyllis Dennery

Some of the key limitations in the study, Dr. Lovasi pointed out, were that it relied on subjects' reports, and their measure did not allow researchers to document timing or the amount of the exposure. Some characteristics could not be measured, such as nutrition during childhood, which Dr. Lovasi said could explain some of the differences the researchers observed. "Also, we only looked at 1 point in time," she said. "We plan to follow the cohort and document how their lungs change over time."

News conference moderator Phyllis Dennery, MD, FAAP, chief of the Division of Neonatology, Children's Hospital of Philadelphia, and professor of pediatrics at the University of Pennsylvania School of Medicine, said: "It's always of interest to go back and see what has an effect down the road on the impact of disease."

The MESA Lung study is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Dr. Lovasi and Dr. Dennery have disclosed no relevant financial relationships.

ATS 2009: American Thoracic Society International Conference: Abstract 280. Presented May 18, 2009.

Source : http://www.medscape.com/viewarticle/703041?sssdmh=dm1.474484&src=nldne

Circumcision reduces the prevalence of high-risk human papillomavirus (HR-HPV) infection and HIV in men, according to studies from South Africa and the USA published in the January 1 issue of the Journal of Infectious Diseases.

Dr. Bertran Auvert from Assistance Publique-Hpitaux de Paris, University of Versailles, France, and his team in South Africa evaluated the effects of male circumcision on HR-HPV infection in a cohort of initially uncircumcised men aged between 18 and 24 years.

A total 637 men who opted for circumcision and 627 uncircumcised controls were followed from 2002-2004 with periodic physical examinations and interviews about their sexual behavior. Urethral swabs were taken from participants at their 21-month visit.

The prevalence of HR-HPV was 23.2% and 14% in the uncircumcised and circumcised groups, respectively, Dr. Auvert's team observed. After adjusting for confounding factors, including HIV status and sexual behavior patterns, circumcision protected from HPV with a prevalence rate ratio of 0.62, they report.

In the second study, Dr. Lee Warner from the US Centers for Disease Control and Prevention, Atlanta, and colleagues evaluated the association of circumcision with a reduced risk of HIV infection in a US population.

The investigators analyzed records of 40,571 visits by heterosexual African American men who took an HIV test in a sexually transmitted diseases clinic in Baltimore.

Dr. Warner's group identified 394 visits by men having a documented exposure to HIV-positive partners. In this sub-group, the prevalence of HIV was over twice as high among uncircumcised men as circumcised men, at 22.0% and 10.2%, respectively, they report.

"The foreskin contains target cells for HIV, herpes and HPV," Dr. Ronald H. Gray, the lead author of a related editorial, explained to Reuters Health. "In addition, the foreskin is vulnerable to ulcers probably as a result of trauma during intercourse, and its removal reduces rates of ulceration by 50%," he added.

"Circumcision is a critical intervention to reduce HIV transmission," Dr. Gray, from the Johns Hopkins Bloomberg School of Public Health, concluded.

Source : http://www.medscape.com/viewarticle/585841

Program Objectives

1. Review the efficacy of insulin therapy for achieving optimal glycemic control in type 2 diabetes
2. Describe barriers to insulin therapy
3. Discuss currently used insulin injection devices and their utility in reducing treatment barriers, and how clinicians can help overcome barriers to achieve successful initiation of insulin therapy
4. Discuss side effects of insulin therapy, such as hypoglycemia and weight gain, and strategies to reduce these effects

Proceed to the Case Simulations

Type 2 diabetes is a complex disease characterized by reduced insulin activity due to abnormalities in insulin secretion and/or action. Most patients also have insulin resistance that creates a need for additional (exogenous) insulin. Glucose metabolism is dysregulated, with increased hepatic glucose production and decreased peripheral glucose uptake leading to hyperglycemia.

Major symptoms of diabetes include extreme hunger, excessive thirst, frequent urination, irritability, increased fatigue, blurry vision, and unusual weight loss. However, because type 2 diabetes comes on gradually, over years as opposed to months or even weeks for type 1, the symptoms for type 2 diabetes may be less prominent. Insulin resistance is associated with abnormalities, such as dyslipidemia and hypertension, which increase the risk for cardiovascular disease in diabetic patients. Elevated triglycerides and decreased high-density lipoprotein (HDL) cholesterol levels are characteristic of type 2 diabetic subjects.

The primary goal of treatment is to lower the glucose level to as close to the normal range as is safe and beneficial to the patient. Glycated hemoglobin [A1C] levels of < 7.0% are considered normal; some patients may benefit from lower levels. To achieve this, insulin therapy is the key treatment for patients with diabetes. Oral or injectable insulin (either basal or bolus) is prescribed depending on the needs of the individual patient. Metformin, an oral agent that suppresses hepatic glucose production, is commonly used as the initial treatment. If needed, a second drug, such as a thiazolidinedione, is added -- which improves insulin sensitivity -- or an insulin secretagogue, such as sulfonylurea.

Barriers to insulin therapy leading to decreased patient adherence include fear of needles, social stigma, and hypoglycemia and weight gain associated with therapy. Clinicians can help patients better manage the disease by reducing these barriers and recommending lifestyle modifications. When individualizing insulin therapy for patients, clinicians must also consider the degree of glucose lowering needed, the side effects associated with drugs, and cost. Further, modification and monitoring cardiovascular risk factors, such as hypertension and lipids, is also critical.

Source : http://cme.medscape.com/viewarticle/576533?src=cme_mp_top

Diagnosis and treatment of attention-deficit/hyperactivity disorder (ADHD) in the primary care setting are reviewed in an article published in the April 15 issue of the American Family Physician.

"...ADHD is a chronic, neurobiologic, behavioral disorder that affects 2 to 16 percent of school-aged children, depending on the diagnostic criteria and population studied (e.g., primary care versus referral)," write Robert Rader, MD, DPh, from Saint Anthony Family Medicine Residency in Oklahoma City, Oklahoma, and colleagues. "The symptoms of ADHD affect cognitive, academic, behavioral, emotional, social, and developmental functioning....Although there are many theories, no single etiology for ADHD has been substantiated."

ADHD is the most frequently diagnosed neurodevelopmental disorder in children and adolescents. Although the pathogenesis of ADHD is still poorly understood, most recent studies have attempted to clarify the role of neurotransmitters including dopamine, norepinephrine, and, most recently, serotonin.

Three general subtypes of ADHD have been identified for purposes of classification: predominantly hyperactive-impulsive, predominantly inattentive, and combined. To facilitate diagnosis and management, screening tools and rating scales have been developed. These include broadband assessments, narrowband assessments, and evaluation of medication adverse effects.

The functioning of the child with ADHD and the quality of life of the patient and family can be dramatically improved with appropriate treatment. A combination of pharmacotherapy and behavioral management is usually recommended.

Pharmacologic treatment includes methylphenidate, mixed amphetamine salts, or other stimulants, and/or nonstimulants such as atomoxetine. There is no evidence supporting the use of 1 stimulant vs another, and short-acting, intermediate-acting, and long-acting preparations have similar effectiveness. Short-acting preparations timed appropriately may facilitate certain activities, whereas long-acting formulations eliminate the need to give medication during school, improve compliance, and decrease opportunity for abuse.

"Treatment should be initiated at low dosages and then titrated over two to four weeks until an adequate response is achieved or unacceptable adverse effects occur," the study authors write. "If one stimulant is not effective, another should be attempted before second-line medications are considered. Although some children benefit from daily psychostimulant therapy, weekend and summer 'drug holidays' are suggested for children whose ADHD symptoms predominantly affect schoolwork or to limit adverse effects (e.g., appetite suppression, abdominal pain, headache, insomnia, irritability, tics)."

Behavioral approaches are also effective, especially those that immediately reward desirable behavior with tokens or points. The efficacy of psychotherapy and cognitive behavioral therapy for the treatment of ADHD has not been tested in high-quality studies.

Key clinical recommendations for practice, and their accompanying level of evidence, are as follows:

• Obtaining information from teachers, family members, and non–family members who are familiar with the child's behavior is essential to properly diagnose ADHD (level of evidence, C).

• The first-line treatment for most patients with ADHD is pharmacologic treatment with stimulant medication (level of evidence, A).

• Compared with intensive behavioral treatment alone, carefully monitored pharmacotherapy is typically more effective for ADHD (level of evidence, B).

• Support groups for parents of children with ADHD facilitate networking with others who have children with similar problems (level of evidence, B).

Combined recommendations from the American Academy of Pediatrics and American Academy of Child and Adolescent Psychiatry (AACAP) for the evaluation of children with suspected ADHD are as follows:

• A child aged 6 to 12 years presenting with inattention, hyperactivity, impulsivity, academic underachievement, or behavioral problems should be evaluated for ADHD by the primary care physician. This evaluation should include the following:

o Standard history and physical examination. The AACAP also recommends evaluating the patient's developmental history, hearing and vision, history of learning difficulties or psychiatric disease illness, and family history of ADHD.

o Neurologic examination

o Family evaluation. The AACAP also recommends assessment of family stressors and family coping style.

o School evaluation.

• Diagnostic and Statistical Manual of Mental Disorders, Fourth Revision (DSM-IV) diagnostic criteria for ADHD must be met to diagnose this condition.

• Information obtained directly from parents or caregivers is needed for accurate diagnosis of ADHD. This should include a description of the main symptoms of ADHD in different settings, age at onset of symptoms, duration of symptoms, and severity of functional impairment.

• Information obtained directly from the classroom teacher, or other school-based professional, should be an important part of the evaluation for ADHD. This should highlight information regarding the core symptoms of ADHD, duration of symptoms, severity of functional impairment, and comorbid conditions. The physician should review all available reports from a school-based multidisciplinary evaluation, including evaluations from the child's teacher or other school-based professional.

• Assessment of a child with ADHD should include workup for comorbid conditions including learning and language disabilities, oppositional defiant disorder, conduct disorder, anxiety, and depression.

• Diagnostic testing in the absence of specific indications is not routinely recommended. Tests that might be appropriate in certain clinical settings include measurement of lead and thyroid hormone levels, neuroimaging, and/or electroencephalography.

In an editor's note, Caroline Wellbery, MD, writes: "As this article was going to press, a study by Molina and colleagues [J Am Acad Child Adolesc Psychiatry. 2009 Epub ahead of print.] was released questioning the long-term effectiveness of ADHD drug therapy. The study showed that there were no significant differences among pharmacologic, behavioral, and combined therapy groups after six to eight years, and that all children in the study had significant impairment compared with unaffected peers."

The review authors have disclosed no relevant financial relationships.

Am Fam Physician. 2009;79:657-665.
Clinical Context

ADHD is a chronic, biologic behavioral disorder that affects 2% to 16% of school-aged children. There is no single cause, but neurotransmitters such as dopamine, norepinephrine, and serotonin have been implicated. Recent studies suggest no association between a child's sex and the disorder.

This is a review of the diagnostic criteria for ADHD and management strategies in children.
Study Highlights

* DSM-IV criteria require that at least 6 of 9 symptoms of either inattention or hyperactivity-impulsivity be met, in discrete settings, and that they be present for more than 6 months, with onset before age 7 years.
* The DSM-IV criteria recognize 3 subtypes: predominantly hyperactive-impulsive, predominantly impulsive, and combined.
* The hyperactive-impulsive subtype is fidgety and restless, on the go, and has difficulty waiting and sitting still.
* The inattentive subtype is easily distracted, forgetful, disorganized with poor concentration, and has difficulty completing tasks.
* The combination subtype exhibits in both types of traits.
* Consequences of ADHD in adolescence include antisocial behavior, cognitive fatigue, legal problems, ineffective self-monitoring, low self-esteem, risk taking, and substance abuse.
* The American Academy of Pediatrics and the AACAP provide 6 recommendations for the evaluation of children suspected of having ADHD.
* The initial evaluation should include history and physical examination, neurologic examination, and family and school assessment.
* Diagnostic testing such as neuroimaging is not routinely recommended.
* DSM-IV criteria should be met before a diagnosis is made.
* Evidence on the core symptoms of ADHD should be obtained directly from parents or caregivers.
* Reports from schools and multidisciplinary reports should be assessed.
* Coexisting conditions such as learning disabilities and conduct disorders should be considered.
* Key recommendations are family and teacher input into assessment, use of stimulant medications as first-line treatment, use of monitored pharmacotherapy, and provision of support groups for parents.
* ADHD is considered a clinical diagnosis and coexists with other conditions.
* Estimated comorbidity rates are 10% to 90% for developmental disorder, 15% to 75% for mood disorder, 35% to 65% for oppositional defiant disorder, 20% to 40% for substance abuse, and 25% for anxiety.
* Stimulants used as first-line treatment include methylphenidate and mixed amphetamine salts with no good evidence to support 1 stimulant vs another.
* Long-acting formulations improve compliance and decrease abuse potential.
* Treatment should be initiated at low doses and titrated during 2 to 4 weeks.
* Weekend and summer drug holidays are suggested to limit adverse effects such as appetite suppression, headache, irritability and tics.
* Serious effects include delays in growth, sudden death, and cardiovascular problems, but these effects are rare.
* Atomoxetine is the first nonstimulant medication approved by the US Food and Drug Administration for ADHD and should be considered if the child does not respond to stimulants or if there is a concern about stimulant abuse.
* Atomoxetine should be discontinued if liver problems or jaundice occurs, and there is a black box warning about suicidal ideation.
* Bupropion is an alternative treatment especially in the presence of mood disorder, but a history of seizure disorder is a contraindication.
* The tricyclic antidepressants imipramine and desipramine can effectively control core ADHD symptoms and should be titrated up.
* Clonidine can be used as a single-dose agent, titrated slowly for 2 to 4 weeks at bedtime.
* Behavioral interventions that have been shown to be useful include rewards for good behavior and consequences for poor behavior, and parental support and training.
* Psychotherapy and cognitive behavioral therapy have no documented efficacy for ADHD.
* Combination pharmacotherapy and behavioral therapy is as effective as pharmacotherapy alone and is more effective than behavioral therapy alone.

Clinical Implications

* The DSM-IV criteria require at least 6 of 9 symptoms to be met for hyperactivity-impulsivity or inattention, duration of more than 6 months, and onset before age 7 years.
* First-line treatment of ADHD is stimulant medications, followed by atomoxetine or antidepressants, and reward and consequences and parental support are used for behavior modification.

Source : http://cme.medscape.com/viewarticle/701882?src=cmemp

May 12, 2009 (Chicago, Illinois) — Research at the University of Iowa's Carver College of Medicine, in Iowa City, has uncovered a link between prematurity, in particular the premature rupture of membranes (PROM), and a single gene (MMP3).

These findings were presented here at the American College of Obstetricians and Gynecologists (ACOG) 57th Annual Clinical Meeting by lead author Heather Byers, BA, a second-year medical student. The paper by Ms. Byers and colleagues was awarded second place among all papers on current clinical and basic investigation submitted to ACOG’s Committee on Scientific Program. Ms. Byers noted that a single-nucleotide polymorphism was found in the gene MMP3, and described the relevance to meeting attendees.

"MMP3 encodes stromelysin," said Ms. Byers, "and degrades the widest array of extracellular molecules within the decidua, fetal membranes, and cervical extracellular matrix. It plays a key role in the proteolytic pathway, in that it activates other matrix metalloproteinases, including MMP1 and MMP9. It is located in a coding region within a group of 4 amino acids, 3 of which are completely conserved," she noted.

Prematurity is defined as being between 20 and 37 weeks and, according to Ms. Byers, is a complex disease without a clear risk case. "It could be due to the fetus, the mother, or the placenta," she told those attending the conference.

It is estimated that approximately 40% of premature deliveries are linked to genetics and familial clustering, with the woman's greatest risks being a previous preterm delivery, having siblings delivered preterm, or having been a preterm child herself.

The majority of premature deliveries (72%) are spontaneous, according to Ms. Byers, and approximately 30% of those are due to PROM. This study was designed to review 4 candidate genes known to be related to PROM: MMP1, MMP3, MMP9, and SERPINH1.

The fetal membranes amnion and chorion derive their strength from fibrillar collagen, and matrix metalloproteinase enzymes break down collagen in the extracellular matrix and fetal membranes. SERPINH1 is a collagen chaperone protein.

DNA samples from premature cases, term controls, and family members in an Argentine population were collected, genotyped, and analyzed. This was done to identify genetic risk factors that might increase the risk for preterm delivery. The data were then compared with data from Iowa families.

As soon as a baby was identified as premature, DNA was collected from cord blood and from the blood or saliva of the parents and maternal grandparents. Sampling was done in the Maternity Hospital in Tucumán, Argentina. Analysis was performed at the University of Iowa.

For every premature baby, the study identified a sex-matched control from a mother without a history of preterm delivery.

Gene expression was assayed with polymerase chain-reaction technology, and 1536 unique DNA samples from 359 families were reviewed. Data were analyzed using the Family-Based Association Test to measure the fetus effect and distribution of Mendelian transmission.

No significant findings were associated with MMP1, MMP9, or SERPINH1. A single-nucleotide polymorphism was found in MMP3. This had a nonsynonymous amino acid change from glutamate to lysine (i.e., from an uncharged to a charged amino acid). The study authors found this to be significant because MMP3 activates other matrix metalloproteinases and degrades the widest array of extracellular molecules in decidua, fetal membranes, and the cervical extracellular matrix.

Ms. Byers is conducting further analyses to map this particular gene and might then separate the findings into preterm delivery, extreme preterm delivery, and late preterm delivery.

Kurt L. Barnhart, MD, MSCE, member of ACOG's Committee on Scientific Program, commented on the results to Medscape Ob/Gyn & Women's Health. Dr. Barnhart is director of women's health research at the University of Pennsylvania in Bryn Mawr, and served as director, with Janice L. Bacon, MD, of the Papers on Clinical and Basic Investigation session.

"This is a very good example of an early basic-science paper looking into some of the causes of this big problem we have, preterm delivery," Dr. Barnhart said. "It looks at some specific gene alterations for a protein that may have to do with integrity of membrane strength. And it found some associations — people with preterm deliveries have altered genetics for that membrane.

So it's more of opening a link to how we can study this and how it may contribute; it's not purporting to be a clinical test at this point, Dr. Barnhart explained. "It's really opening a window of investigation for us to understand the pathway. Eventually, hopefully, we will have some specific information that can be developed into a diagnostic test," he said.

The study was funded by Carver College of Medicine, the National Institutes of Health, and the March of Dimes. Ms. Byers disclosed no relevant financial relationships.

Source : http://www.medscape.com/viewarticle/702684?sssdmh=dm1.470812&src=nldne

May 12, 2009 (Chicago, Illinois) – Evidence is accumulating rapidly that a particular region of the human genome is associated with the development of autism. This information could help enormously in the development of treatments for the condition.

In a study presented here at the 8th Annual International Meeting for Autism Research and published online April 28 in the Annals of Human Genetics, a team of researchers found a clustering of mutations associated with autism in a region known as 5p14.1.

Another study, by some of the same researchers, published online April 28 in Nature, also linked his region with autism spectrum disorders. Located very close to this region are 2 genes coding for proteins known as cadherins that are involved in adhesion of neurons; these, in turn, are implicated in autism pathogenesis.

This is the first time that a particular gene region has been implicated in autism. "Our identification and replication of common variation [in families affected by autism] on chromosome 5p14.1 is a promising development in the struggle to understand the genetics of autism," said Margaret Pericak-Vance, PhD, lead investigator of the study published in the Annals of Human Genetics and a coauthor on the Nature paper. "Further functional analyses are needed to figure out the potential molecular mechanisms," she told Medscape Psychiatry.

Geraldine Dawson, PhD, the chief scientific officer for Autism Speaks and a coauthor of the Nature paper, notes that the convergence of findings from these 2 large-scale studies increases the likelihood that the 5p14.1 locus is, indeed, implicated in autism.

"However, keep in mind that this is going to be 1 of many [gene regions] that contribute to autism," said Dr. Dawson. "But this is 1 that now has been replicated and again points to specific aspects of brain function that we know are affected in autism. Ultimately, the goal will be to understand how these genes affect the biochemistry of the brain, so we can develop medications that could potentially repair that aspect of brain function."

The study led by Dr. Pericak-Vance, from the University of Miami's Miller School of Medicine, in Florida, involved the genotyping of 438 white families affected by autism and a comparison with the mutation locations found in another 457 white families who are part of the Autism Genetics Resource Exchange database.

Sophisticated DNA analyses revealed a clustering of mutations associated with autism risk in the 5p14.1 region. None of the mutations occurs within a known gene or a genetic sequence known to regulate a gene.

However, the investigators determined that lying nearby are several regions of potential relevance to autism, including the gene sequences coding for cadherin-9 and cadherin-10, a group of proteins involved in cell-cell junctions in the nervous system.

In the study published in Nature, Drs. Dawson, Pericak-Vance, and 54 coinvestigators performed similar, genomewide studies on 780 families with affected children, 1204 individuals affected by autism, and 6491 healthy controls. They found a clustering of genetic variants in the 5p14.1 region.

The study was supported by the National Institutes of Health and the Hussman Foundation. Dr. Pericak-Vance has no conflicts of interest to disclose.

Source : http://www.medscape.com/viewarticle/702685?sssdmh=dm1.470812&src=nldne

May 12, 2009 (Chicago, Illinois) – Peer support and one-on-one therapist guidance appear to be particularly effective in helping children with autism form friendships with their classmates.

In a rare, randomized, head-to-head trial, peer support alone or in combination with one-on-one guidance proved to help children with autism more than guidance alone or neither peer support nor guidance.

This points to a way that children can be included in regular classrooms rather than being relegated to special-education classes or having help from shadow teachers, lead investigator Connie Kasari, PhD, from the University of California, Los Angeles, told Medscape Psychiatry.

"And the good news is we can make differences in a short period of time," added Dr. Kasari.

The study was presented here at the 8th Annual International Meeting for Autism Research (IMFAR), Dr. Kasari and colleagues randomized 15 children with autism spectrum disorders (ASD) to each of these 4 approaches. There were a total of 54 boys and 6 girls, all of whom were in general-education classrooms. The participants' average age was 8 years and average IQ was 91.

Children randomized to one-on-one guidance had 2 sessions per week of direct instruction by a therapist in appropriate interaction with other children. Those randomized to peer support were given 2 sessions per week with 3 peers, each of whom was trained to help children with autism learn how to be a good friend and to include others in their play activities.

Children with ASD who had both one-on-one guidance and peer support had 2 sessions of each per week. The fourth group was given neither guidance nor peer support, but some of the children had outside aides or school aides and/or attended other social groups geared to helping them improve their social skills. Each of the approaches was used for 6 weeks.

After 6 weeks, the ASD children and other children were asked who played with whom on the playground. In addition, the children were asked who their top 3 friends were. The investigators used this information to determine whether children with ASD improved their ability to play with others and make friends.

Feelings of Friendship Reciprocated

The results revealed that significantly more children with ASD felt they had developed friendships after the study. Moreover, significantly more of these feelings of friendship were reciprocated by their non-ASD classmates.

Dr. Kasari and her coinvestigators also found that children with ASD who had received the combination of one-on-one therapist guidance and peer support improved their development of these social networks and increased their number of friends more than those with one-on-one guidance alone or with neither guidance nor peer support. The extent of improvement among children receiving the combination was the same as among those who received peer support alone.

In addition, teachers rated ASD children who had received peer support alone as having undergone the greatest positive change, while the clinicians involved in the study rated the peer-only and combination subjects as having undergone the greatest improvement in friendships.

Edwin Cook, Jr., MD, from the University of Illinois at Chicago's College of Medicine, commented that while the study involved only a small number of children, "the significant improvement in social networks for children with ASD was strong enough to be seen in a group of 15 compared with controls." He added that studies with larger numbers of subjects will help confirm these results.

The study was supported by the National Institutes of Health and the National Institute of Mental Health. Dr. Kasari has no conflicts of interest to disclose.

Source : http://www.medscape.com/viewarticle/702694?sssdmh=dm1.470812&src=nldne

May 11, 2009 (Chicago, Illinois) — Researchers have come up with a relatively simple tool that could be the answer to many clinicians' wish for a practical screen for autism in very young children. Called the Systematic Observation of Red Flags (SORF), the instrument distinguishes between 18- to 24-month-olds with autism spectrum disorders (ASDs) and those with either developmental delays or who are healthy, normal children.

A study presented here at the 8th Annual International Meeting for Autism Research indicates that children who have at least eight of the 20 "red flags" in SORF have a high probability of having autism.

In 2007, members of the American Academy of Pediatrics' Council on Children With Disabilities called for pediatricians to systematically screen all infants for ASDs at 18 and 24 months of age (Johnson CP et al. Pediatrics. 2007;120:1183-1215).

However, there were no reliable physician-administered tools for ASD screening of the general infant population; the Modified Checklist for Autism in Toddlers (M-CHAT) and the Infant-Toddler Checklist (ITC) are usually relied upon for first-line, parent-reported screening. The SORF could help fill that gap, notes Geri Dawson, PhD, chief scientific officer for Autism Speaks.

"This is like a second-level screening; it complements the M-CHAT," Dr. Dawson told Medscape Psychiatry. "The main point is that it's very exciting to see a screening tool being developed that can be easily used in pediatricians' offices, so these kids can be identified early and can get into early intervention, so they can get the best outcomes possible."

Not All "Red Flags" Useful

Lead investigator Amy Wetherby, PhD, from Florida State University, in Tallahassee, and colleagues published a paper last year on a study of the combined use of the ITC and a clinician-administered, videotape-based screener called the Communication and Symbolic Behavior Scale Developmental Profile (CSBS DP) Behavior Sample (Wetherby AM et al. Autism. 2008;12:487-508).

The CSBS DP Behavior Sample involves a warm-up of about 10 minutes and a 30- to 40-minute videotaped session in which the infant is tested for communication and comprehension abilities.

The team selected its subjects from a pool of 6581 children recruited by the Florida State University FIRST WORDS Project. The children's parents were asked to complete the ITC, which has 24 questions about the child's developmental milestones and 1 question about whether the parent is concerned about the child's development. The ITC provides a first-line indicator of whether the child is at risk for communication delay; it does not determine whether a child has ASD.

Next, parents whose children screened positive on the ITC or who responded in the affirmative to the ITC question about concerns about the child's development underwent the CSBS DP Behavior Sample videotaping session. The investigators reviewed the videotapes and scored the children for the presence of 29 "red flags." This takes about 30 minutes per videotape.

They found that 9 of the 29 red flags were not useful in discriminating between children with and without ASDs. Therefore, they focused on the remaining 20 red flags as true indicators of the presence of ASDs and dubbed this constellation the SORF.

These 20 items probe for the presence of impairment in social interaction, repetitive behaviors and fixated interests, impairment in communication, and difficulties with emotional regulation. A child can score from zero to 2 for each of the red flags; hence the highest possible score on the SORF is 40 and the lowest is zero.

Quicker Screening Tool?

Dr. Wetherby and her coinvestigators found that a score of 10 or more on the SORF yields a sensitivity of 0.87 for an ASD diagnosis. The specificity is 0.81, the positive predictive value is 0.76, and the negative predictive value is 0.94.

They also found that the presence of eight red flags is also a useful cutoff for ASD; it has a sensitivity of 0.87, a specificity of 0.84, a positive predictive value of 0.79, and a negative predictive value of 0.91. A total of 60 children in their sample were found to have ASD.

A check of correlations with other ASD measures, such as the gold-standard Autism Diagnostic Observation Schedule, showed very high levels of agreement between these and the SORF for both the subjects' total score from the 20 items and the total number of red flags.

"We are beginning to study a checklist of fewer than 20 of the red flags to compare with our more detailed list," said Dr. Wetherby. "If it achieves the same accuracy, then we can use this as a quicker screening measure. But we don't yet know if that is feasible."

The study is supported by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health, the Centers for Disease Control and Prevention, and the US Department of Education. Dr. Wetherby discloses that as an author of the Communication and Symbolic Behavior Scales, she receives royalties on the sales of the test.

Source : http://www.medscape.com/viewarticle/702626?sssdmh=dm1.470812&src=nldne