Quick Take: Preventing Recurrent Clostridium difficile Infection with Bezlotoxumab

Posted on January 26, 2017 by gutsandgrowth

A recent study on a new monoclonal antibody to prevent Clostridium difficile infection is available from the NEJM. Here’s the link: Preventing Clostridium difficile Infection Recurrence

My take: In Modify I and Modify II, Bezlotoxumab reduced the rate of Clostridium difficile recurrence in elderly patients (median age 66 years). In a high risk patients, the likely hefty cost of this medication may be warranted.

These studies were likely pivotal in receiving FDA approval: FDA Approves Merck’s ZINPLAVA™ (bezlotoxumab) to Reduce Recurrence of Clostridium difficile Infection

Constipation Video from Primary Children’s Hospital

Posted on January 25, 2017 by gutsandgrowth

This is a really good educational video (< 8min) -now on YouTube: Constipation in Children: Understanding and Treating This Common Problem (Thanks to John Pohl’s twitter feed for this resource)

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Cost Effectiveness & Underpowered Studies

Posted on January 24, 2017 by gutsandgrowth

A recent study (ALT Ma et al. J Pediatr 2016; 179: 216-8) reaches a conclusion that questions the cost-effectiveness of pretreatment TPMT activity in pediatric patients. In my opinion, this retrospective study is ridiculous. Here’s why:

The authors examined thiopurine transmethyltransferase (TPMT level) in 228 children before starting a thiopurine. They found the following:

Only 2 patients experienced mild neutropenia
12% of their cohort had intermediate activity and 88% normal TPMT activity

I agree with their conclusion that routine blood tests are needed following institution of thiopurines, I think stating that “from an economic point of view –the cost for testing TPMT enzyme activity was high without major clinical benefit” cannot be made with such a small study. Deficient TPMT activity occurs in about 1 in 300. If a single patient develops bone marrow suppression due to a thiopurine medication, this can lead to a horrific and prolonged hospitalization. The cost of such a hospitalization, both economically and emotionally, is enormous.

My take: If I were taking a thiopurine, I would want to know if I metabolized this medication at a slower rate and was at increased risk for bone marrow suppression. My hunch is the authors would not forgo checking a TPMT level on themselves despite their study’s conclusion, particularly if they have ever witnessed a patient with thiopurine-induced bone marrow suppression.

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Grand Prismatic Spriing, Yellowstone

Briefly noted: PFAPA Study

Posted on January 23, 2017 by gutsandgrowth

U Lantto et al. J Pediatr 2016; 179: 172-7. This retrospective study showed that tonsillectomy was highly effective in children with PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) -both those with classic features and incomplete features.

“In the group that met Thomas criteria, 97% (56/58) had complete resolution of fever episodes after tonsillectomy; in the group that did not meet Thomas criteria (50/50) had complete resolution.”

Thomas criteria:

Recurring fevers with early age of onset (<5 years) [the authors suggest a minimum of 5 episodes]
Constitutional symptoms in the absence of over upper respiratory infection with at least one of the following: aphthae, cervical adenitis, pharyngitis
Exclusion of cyclic neutropenia
Completely asymptomatic interval between episodes
Normal growth and development

Quick Take on Migraine Study

Posted on January 22, 2017 by gutsandgrowth

For those who missed this important pediatric study, a quick take ~2 min video link: Pediatric Migraine CHAMP Study

My take: It looks like placebo did pretty well with >60% response rate. In a commentary on this subject, the authors noted that when patients are seen by the physician, the symptoms are often severe. So, some improvement is expected, in part, due to regression to the mean; that is, it is common to return to their baseline level of symptoms.

How Rudeness Affects Performance in Medicine (and probably elsewhere)

Posted on January 21, 2017 by gutsandgrowth

From A Riskin et al. Pediatrics Jan 2017 (Thanks to Seth Marcus for pointing out this study), Link: Rudeness and Medical Team Performance

Abstract

OBJECTIVES: Rudeness is routinely experienced by medical teams. We sought to explore the impact of rudeness on medical teams’ performance and test interventions that might mitigate its negative consequences.

METHODS: Thirty-nine NICU teams participated in a training workshop including simulations of acute care of term and preterm newborns. In each workshop, 2 teams were randomly assigned to either an exposure to rudeness (in which the comments of the patient’s mother included rude statements completely unrelated to the teams’ performance) or control (neutral comments) condition, and 2 additional teams were assigned to rudeness with either a preventative (cognitive bias modification [CBM]) or therapeutic (narrative) intervention. Simulation sessions were evaluated by 2 independent judges, blind to team exposure, who used structured questionnaires to assess team performance.

RESULTS: Rudeness had adverse consequences not only on diagnostic and intervention parameters (mean therapeutic score 3.81 ± 0.36 vs 4.31 ± 0.35 in controls, P < .01), but also on team processes (such as information and workload sharing, helping and communication) central to patient care (mean teamwork score 4.04 ± 0.34 vs 4.43 ± 0.37, P < .05). CBM mitigated most of these adverse effects of rudeness, but the postexposure narrative intervention had no significant effect.

CONCLUSIONS: Rudeness has robust, deleterious effects on the performance of medical teams. Moreover, exposure to rudeness debilitated the very collaborative mechanisms recognized as essential for patient care and safety. Interventions focusing on teaching medical professionals to implicitly avoid cognitive distraction such as CBM may offer a means to mitigate the adverse consequences of behaviors that, unfortunately, cannot be prevented.

This same group had a related study in 2015:The Impact of Rudeness on Medical Team Performance: A Randomized Trial

My take:The saying “you catch more flies with honey than you do with vinegar” is probably accurate.

Costa Maya, Mexico

Role of Biosimilars in Inflammatory Bowel Disease

Posted on January 20, 2017 by gutsandgrowth

A cautionary note on biosimilars has been discussed in a recent review (DT Rubin et al. Gastroenterol & Hepatol 2016; 12: 741-51)

In the recently completed NOR-SWITCH study presented at the United European Gastroenterology Week 2016 meeting, “a total of 481 patients were recruited across 40 centers: all patients had been on stable treatment with the originator infliximab for at least 6 months…When looking specifically at IBD patients, disease worsening was noted in 21.2% of originator infliximab-treated patients and 36.5% of CT-P13-treated Crohn’s disease patients (n=155).” The 15% difference did not reach statistical significance, but is concerning. The authors state that “subtle postranslational modifications unique to the biosimilars may be sufficient to lead to antidrug antibody formation with associated loss of response. Also, it is noted that this study did not include endoscopic evaluation.

The authors note that therapeutic monitoring worked with biosimilar product using available infliximab assays.

My take: We still have a lot to learn. The preliminary message, until more studies are available, indicate that switching stable patients could increase risk of losing response.

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Puerto Rico

Standardizing the Care of Children Receiving Chronic Glucocorticoid Therapy

Posted on January 19, 2017 by gutsandgrowth

A recent study (ML Basiaga et al. J Pediatr 2016; 179: 226-32) highlights the large variation in care for 701 children receiving steroids (for at least 15 days) at a leading children’s hospital (CHOP). I think, given the fact that this is a retrospective study and the huge variation in steroid exposure, the message regarding variation should not be taken that seriously. But, the article does suggest that in children with chronic glucocorticoid therapy, several measures should be considered:

Bone health -particularly Vitamin D (25-OH) levels
Immunity -particularly assuring pneumococcal and influenza vaccines
Lipid screening
Stress steroid plan. The authors indicate that the endocrinology society recommendations have included instructing parents in intramuscular hydrocortisone in case of vomiting or severe stress.

My take: Having a standard approach to an at-risk group makes sense, however, “whether implementation of preventive care guidelines improves outcomes in children” is not known.

Is It OK for Pediatricians to try to Prevent Firearm Injuries? Focus on Child Safety –Not on Gun Safety

Posted on January 18, 2017 by gutsandgrowth

A recent study (JM Garbutt et al. J Pediatr 2016; 179: 166-71 and related editorial by MD Dowd, pg 15-17) provide relevant information on the issue of firearm injury prevention.

The study describes the results of a survey provided to 1246 parents at a diverse group of practices around St Louis.

Key findings:

36% reported being owners of firearms
Of the owners, 25% reported ≥1 firearm was stored loaded and 17.9% carried a firearm when leaving the house.
75% of all parents thought pediatricians should provide advise on safe storage of firearms (71% of owners); however, only 12.8% of all parents reported a discussion about firearms with the pediatrician

The discussion and commentary on this study are more interesting than the actual results. Key points:

The AAP has recommended that pediatricians screen for the presence of household firearms and has stated that a “home without guns is the safest option…Advising safe storage is also encouraged.” Prior surveys have echoed this study that few pediatricians counsel families about firearm safety.
Despite AAP recommendations, over “60% of Americans believe that a ‘gun in the house makes it safer’ which is a more common attitude than in 2004 when 42% of Americans held that view.
Providing a child with firearm avoidance educational programs (eg. NRA’s “Eddie Eagle”) “is unlikely to lead to safe behaviors…[and] may give parents a false sense of security.”
“Children cannot distinguish real guns from toy guns and are strong enough to pull a trigger as early as 3 years of age.”
Approaching the topic of safe storage “as an expert in child development” and children’s unpredictable behavior rather than in firearm safety “may be acceptable to both pediatricians and parents.”
The authors advocate keeping firearm storage on a checklist of hazards (eg. medication storage, avoiding household poisons) –though this has not been well-studied.
From editorial: “When compared with other developed nations, US children under 15 years of age are 12 times more likely to be killed by a gun…We know that nearly 1 in 10 families with guns admit to keeping at least 1 gun loaded and unlocked, and nearly one-half keep at least 1 gun unlocked.”

So, in fact, having a gun in the home does not make a home safer, just the opposite. But delving into this topic is probably not productive due to strong feelings tangential to gun ownership. There have been unsuccessful legislative efforts in over 10 states to prevent physicians from discussing the topic as well as a protracted legal battle in Florida.

My take (borrowed from editorial): “Although the difference between “gun safety” and “child safety” may seem subtle, such a shift allows a consistent approach to home injury prevention across mechanisms of injury with the focus on the child, not the gun.” “Little children are curious and big children (teens) are impulsive, so exposure to unsecured guns can lead to tragic outcomes that cannot be prevented by child education. Who better to deliver this message than pediatricians?”

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New HCV Treatment Effective in Adolescents –Important Study Now Published Online

Posted on January 17, 2017 by gutsandgrowth

A soon-to-be-published study (available online Hepatology) from WF Balistreri et al shows that the combination of Ledipasvir-Sofosbuvir is highly effective in pediatric patients aged 12-17 years.

Here is the abstract:

ABSTRACT

No all-oral, direct-acting antiviral regimens have been approved for children with chronic hepatitis C virus (HCV) infection. We conducted a Phase 2, multi-center, open-label study to evaluate the efficacy and safety of ledipasvir–sofosbuvir in adolescents with chronic HCV genotype 1 infection. One hundred patients ages 12 to 17 years received a combination tablet of 90 mg ledipasvir and 400 mg sofosbuvir once daily for 12 weeks. On the 10th day following initiation of dosing, 10 patients underwent an intensive pharmacokinetic evaluation of the concentrations of sofosbuvir, ledipasvir, and the sofosbuvir metabolite GS-331007. The primary efficacy endpoint was the percentage of patients with a sustained virologic response 12 weeks posttreatment (SVR12). Median age of patients was 15 years (range, 12-17 years). A majority (80%) were HCV treatment naïve, and 84% were infected through perinatal transmission. One patient had cirrhosis and 42 did not; in 57 patients the degree of fibrosis was unknown. Overall, 98% (98/100; 95% CI, 93% to 100%) of patients reached SVR12. No patient had virologic failure. The 2 patients who did not achieve SVR12 were lost to follow-up either during or after treatment. The 3 most commonly reported adverse events were headache (27% of patients), diarrhea (14%), and fatigue (13%). No serious adverse events were reported. AUCtau and Cmax values for sofosbuvir, ledipasvir, and GS-331007 were within the predefined pharmacokinetic equivalence boundaries of 50% to 200% when compared with adults from Phase 2 and 3 studies of ledipasvir and sofosbuvir. Conclusion: Ledipasvir−sofosbuvir was highly effective in treating adolescents with chronic HCV genotype 1 infection. The dose of ledipasvir−sofosbuvir currently used in adults was well tolerated in adolescents and had an appropriate pharmacokinetic profile.

My take: This is great news for pediatric patients. This study indicates that this breakthrough therapy (and likely others) for adults will become more widely available for pediatric patients soon.

TV sports analysts have tremendous insight! Virginia needs to score enough points to win.