Pharmaceutical Prescription Practices Tied to Pharmaceutical Payments to Doctors

Posted on March 25, 2016 by gutsandgrowth

A recent buzz has developed regarding a ProPublica study showing an association between the amount of money physicians receive from pharmaceutical companies and their likelihood of recommending brand (rather than generic) prescription drugs.

Here’s a link to the full story: Now There’s Proof: Docs Who Take Company Cash Tend to Prescribe More Brand-Name Meds

“The more money doctors receive from drug and medical device companies, the more brand-name drugs they tend to prescribe, a new ProPublica analysis shows. Even a meal can make a difference.”

Here’s a link to NPR’s summary: Drug-Company Payments Mirror Doctors’ Brand-Name Prescribing An excerpt:

“A ProPublica analysis has found that doctors who receive payments from the medical industry do indeed prescribe drugs differently on average than their colleagues who don’t. And the more money they receive, the more brand-name medications they tend to prescribe.

We matched records on payments from pharmaceutical and medical device makers in 2014 with corresponding data on doctors’ medication choices in Medicare’s prescription drug program.

Doctors who got money from drug and device makers prescribed a higher percentage of brand-name drugs overall than doctors who didn’t, our analysis showed. Even those who simply got meals from companies prescribed more brand-name drugs, on average.”

My take: Prescription patterns vary widely among physicians and often for good reason. At the same time, it is likely that in many cases variation in prescription patterns is influenced by frequent contact with pharmaceutical companies. As a consequence, this has the potential to make patients question whether their physician always has their best interest in mind and the potential to increase healthcare costs.

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Is Intestinal Function in Children with Autism Different?

Posted on March 24, 2016 by gutsandgrowth

There has been a lot of concern that abnormal GI function contributes to both behavioral and gastrointestinal symptoms in children with autism. To categorize some of these problems, the term ‘leaky gut’ has been used.

An upcoming study (RI Kushak et al. JPGN DOI: 10.1097/MPG.0000000000001174) (thanks to Ben Gold for forwarding this reference) examines this issue. Using a case-control design, pediatric patients with autism spectrum disorder (ASD) (n=61) were compared with 50 children with normal development.

Workup:

Endoscopy (EGD and colonoscopy) with histologic analysis
Disaccharidase analysis
Intestinal permeability studies with lactulose and rhamnose
Fecal biomarkers: calprotectin and lactoferrin

According to the authors, all of the study subjects underwent endoscopy and “all had clinical indications for diagnostic endoscopy.” Most common indications were parental reports of abdominal pain and diarrhea.

Key findings:

Disaccharidase activity levels were not significantly different between the groups. In agreement with prior studies, there was frequent lactase deficiency, with 66% of ASD children in this study with deficient enzyme activity (<15 μmol/min/g). However, lactase activity in the children with ASD was not lower than the non-ASD children.
There were no significant differences in measures of intestinal permeability. Normative values for lactulose and rhamnose ratio are not definitively established. However, when using similar cutoff ratios, there were similar results in both groups.

Calprotectin:

Intestinal inflammatory markers (calprotectin/lactoferrin) were not significantly different, after the authors excluded the five “neurotypical” children who were diagnosed with inflammatory bowel disease.
For calprotectin, the authors considered a level <50 mcg/g to be normal. In the ASD group, 31of 49 (63%) had abnormal calprotectin compared with 19 of 31 (61%) in the non-ASD group.
For calprotectin levels >150 mcg/g, 9 of 49 (18%) reached this level in the ASD group and 8 of 31 (26%) in the non-ASD group.

Histology:

Similar levels of GI tract inflammation were noted in both groups –generally mild.
In the ASD group, 32 (52%) had inflammation somewhere in their GI tract, “but it was generally mild and non-diagnostic.” In the ASD group, five had features consistent with GERD, two had eosinophilic esophagitis (EoE). There were 12 (19%) who had colonic inflammation and 3 (5%) with ileal inflammation. None had celiac disease or H pylori.
In the non-ASD group, four had EoE, four (8%) had ileal inflammation, and nine (18%) had colonic inflammation. The authors noted Crohn’s disease in three and a total of five children with IBD.

My take:

This study suggests that symptomatic children with autism have similar (and probably not worse) GI problems as neurotypical children. The idea that children with autism have a more leaky gut than children without autism is quite dubious based on these results.
The biggest problem for GI physicians is not addressed in this study and involves children with and without autism: appropriate selection for evaluation. While the authors chose children with “clinical indications,” these, in fact, are often subjective and with permissive interpretation could be used to justify endoscopy in 40% of children.
Another huge problem is interpretation of abnormal results. While the authors report large numbers with intestinal inflammation in both groups, most of this was considered to be insignificant clinically. How should trivial inflammation be reported in studies? This problem is not unique to this study and makes it difficult to assess the value of endoscopy more broadly.

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Detrimental Effect of Early Parenteral Nutrition in Critically-ill Children

Posted on March 23, 2016 by gutsandgrowth

Ahead of publication: T Fizez et al. Early versus Late Parenteral Nutrition in Critically Ill Children. DOI: 10.1056/NEJMoa1514762

Link to quick take video summary (<2 minutes) : NEJM Quick Take on Parenteral Nutrition in Children

Abstract:

BACKGROUND

Recent trials have questioned the benefit of early parenteral nutrition in adults. The effect of early parenteral nutrition on clinical outcomes in critically ill children is unclear.

METHODS

We conducted a multicenter, randomized, controlled trial involving 1440 critically ill children to investigate whether withholding parenteral nutrition for 1 week (i.e., providing late parenteral nutrition) in the pediatric intensive care unit (ICU) is clinically superior to providing early parenteral nutrition. Fluid loading was similar in the two groups. The two primary end points were new infection acquired during the ICU stay and the adjusted duration of ICU dependency, as assessed by the number of days in the ICU and as time to discharge alive from ICU. For the 723 patients receiving early parenteral nutrition, parenteral nutrition was initiated within 24 hours after ICU admission, whereas for the 717 patients receiving late parenteral nutrition, parenteral nutrition was not provided until the morning of the 8th day in the ICU. In both groups, enteral nutrition was attempted early and intravenous micronutrients were provided.

RESULTS

Although mortality was similar in the two groups, the percentage of patients with a new infection was 10.7% in the group receiving late parenteral nutrition, as compared with 18.5% in the group receiving early parenteral nutrition (adjusted odds ratio, 0.48; 95% confidence interval [CI], 0.35 to 0.66). The mean (±SE) duration of ICU stay was 6.5±0.4 days in the group receiving late parenteral nutrition, as compared with 9.2±0.8 days in the group receiving early parenteral nutrition; there was also a higher likelihood of an earlier live discharge from the ICU at any time in the late-parenteral-nutrition group (adjusted hazard ratio, 1.23; 95% CI, 1.11 to 1.37). Late parenteral nutrition was associated with a shorter duration of mechanical ventilatory support than was early parenteral nutrition (P=0.001), as well as a smaller proportion of patients receiving renal-replacement therapy (P=0.04) and a shorter duration of hospital stay (P=0.001). Late parenteral nutrition was also associated with lower plasma levels of γ-glutamyltransferase and alkaline phosphatase than was early parenteral nutrition (P=0.001 and P=0.04, respectively), as well as higher levels of bilirubin (P=0.004) and C-reactive protein (P=0.006).

CONCLUSIONS

In critically ill children, withholding parenteral nutrition for 1 week in the ICU was clinically superior to providing early parenteral nutrition. (Funded by the Flemish Agency for Innovation through Science and Technology and others; ClinicalTrials.gov number, NCT01536275.)

More details:

Methods:

“In both study groups, enteral nutrition was initiated early and was increased in accordance with local guidelines. Both study groups also received intravenous micronutrients (trace elements, minerals, and vitamins) starting from day 2 and continuing until the enteral nutrition provided reached 80% of the caloric targets. Starting from the morning of day 8 in the pediatric ICU, supplementary parenteral nutrition was provided for patients in both groups who were not yet receiving 80% of the caloric target enterally.”
45% of patients were less than 1 year of age

Discussion:

“Late parenteral nutrition resulted in fewer new infections, a shorter duration of dependency on intensive care, and a shorter hospital stay. The clinical superiority of late parenteral nutrition was shown irrespective of diagnosis, severity of illness, risk of malnutrition, or age of the child.”

My take: The concept of providing early aggressive nutrition is NOT supported by this study; this study shows that early parenteral nutrition may be detrimental in critically-ill children. This study echoes the results of a similar study in adults: Early versus late parenteral nutrition in critically ill adults

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Torsion of Accessory Spleen

Posted on March 22, 2016 by gutsandgrowth

A case report (PM Guglietta et al. NEJM 2016; 374; 373-82) presents a 9 year-old girl who had repeated episodes of abdominal pain with associated nonbilious vomiting. These pains started 5 years prior and were often sudden episodes of sharp pain on the left side or epigastric region and were associated with tachycardia.

AXR in Case Report

Ultimately the diagnosis was established with a CT scan. “Most persons with accessory spleens are asymptomatic, but abdominal pain can occur with torsion.”

While the case report is interesting, one aspect I did not like was the discussants justification of the delay of the diagnosis based on the presumption of constipation. The radiologist even commented: “a moderate-to-abundant amount of stool distributed in the colon, particularly the ascending colon; these findings are consistent with the clinical history of constipation.” This and other comments in the case study go against previous expert recommendations to avoid routine radiographs in the diagnosis of constipation and the finding of reviews which have not found a correlation between clinical symptoms and so-called fecal loading on abdominal radiographs.

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What happens with 98,500 IU/day of Vitamin A

Posted on March 21, 2016 by gutsandgrowth

An interesting case report (LA Beste et al. NEJM 2016; 374: 73-8) reviews the presentation of a previously healthy 54 year old with ascites. He initially indicated that he was taking 100 IU per day of vitamin A (his current dose), but later on directed questioning admitted that he had averaged 98,500 IU/day for prior 6 months.

The clinical-problem solving case reviews useful pointers about portal hypertension and in particularly noncirrhotic portal hypertension. Vitamin A is a rare cause of noncirrhotic portal hypertension.

Other causes of noncirrhotic portal hypertension:

Prehepatic level: portal vein or splenic vein thrombosis, splanchnic arteriovenous malformation
Intrahepatic level: hepatic vasculitis, HIV infection, infiltrative disease, and medications
Posthepatic: Budd-Chiari syndrome, IVC obstruction, restrictive cardiac disease.
Worldwide, schistosomiasis is the most common reason.
When other causes have been excluded, idiopathic noncirrhotic portal hypertension may be diagnosed, “especially in patients with chronic infection, thrombophilia, and immunologic conditions such as SLE.” In one series of 69 patients, the diagnosis of idiopathic noncirrhotic portal hypertension was delayed for more than a year in 25% of cases and 7% received an erroneous diagnosis of cryptogenic cirrhosis.

Other points:

When ascites is due to cirrhosis, other signs of liver disease are typically present, including jaundice and laboratory findings (low albumin, coagulopathy, hyperbilirubinemia) as well as absence of cirrhosis on biopsy.
Serum retinol levels poorly reflect total body stores of vitamin A (& was normal in this patient)
Vitamin A supplementation in appropriate doses can prevent blindness in areas where food stores are not secure. But, consuming excessive doses can lead to being a case report.

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Excess Childhood Salt Intake Associated with Obesity

Posted on March 20, 2016 by gutsandgrowth

A recent study (C Grimes et al. 24-h urinary sodium excretion is associated with obesity in a cross-sectional sample of Australian schoolchildren British Journal of Nutrition Volume 115 / Issue 06 / March 2016, pp 1071 – 1079) was summarized at AJP.com.au: Childhood salt intake linked to obesity.

An excerpt:

The study also found that in both four-to-seven-year olds and eight-to-12-year-olds, the prevalence of abdominal obesity was also higher in children with a higher intake of salt.

The recent findings published in the British Journal of Nutrition came from the SONIC (Salt and Other Nutrient Intakes in Children) study that measured salt intake in 666 primary schoolchildren aged four to 12 years….

“We found that 70% of Australian children are eating over the maximum amount of salt recommended for good health.

“In this study children were eating on average six grams of salt a day, which is over a teaspoon, and they should be aiming to eat about 4-5 grams a day.

”For every additional gram of salt children ate this was associated with a 23% greater likelihood of being overweight or obese. Such high intakes of salt are setting children up for a lifetime risk of future chronic disease such as high blood pressure and heart disease”

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21 Year Data for Cancer Survivors

Posted on March 19, 2016 by gutsandgrowth

Most pediatric gastroenterologists see many children with pediatric cancers, so it is gratifying to see data showing improving long-term outcomes (GT Armstrong et al. NEJM 2016; 374: 833-42). In addition, pediatric oncology serves as a model for improving therapy by enrolling virtually all of its patients in research protocols.

The authors evaluated late mortality among 34,033 patients in the Childhood Cancer Survivor Study. All of these patients had survived at least 5 years after childhood cancer. During the study which had a median followup of 21 years, there were 3958 deaths and 1618 (41%) of these were attributable to health-related causes, including subsequent neoplasms (n=746), cardiac (n=241), and pulmonary (n=137).

The improvement in treatment regimens have included reductions in radiotherapy and anthracycline exposure. The graph below shows survival rates 20 years after being cancer-free (15 years after being cancer-free for 5 years).

My take: This study confirms that these improved regimens have long-lasting effects on mortality. Through cooperative research, we can do better in oncology and in all of pediatrics.

Incidence of death from any cause from patients treated between 1970-1999.

Bad News Bili

Posted on March 18, 2016 by gutsandgrowth

A study (BL Schneider et al. J Pediatr 2016; 170: 211-7) from ChiLDReN (Childhood Liver Disease Research Network) shows that infants with biliary atresia whose total bilirubin (TB) does not drop below 2 mg/dL (34.2 microM) at anytime during the first 3 months after hepatoportoenterostomy (HPE) (Kasai) are at high risk for disease progression.

Key findings:

68/137 (50%) had TB <2.0 at some point following HPE.
In the cohort with TB ≥ 2.0, the odds ratio for liver transplantation or death was 16.8. Higher TB was associated with diminished weight gain, coagulopathy, and hypoalbuminemia
In the cohort with TB ≥ 2.0, transplant-free survival at 2 year occurred in only 20% compared with 86% in the TB <2.0 group
Interestingly, only 6.6% had variceal bleeding among the entire cohort by age 2 years.

The TB was associated with multiple other parameters of worsening liver function, indicating that TB is not the only measure to affect the decision of liver transplantation.

My take: About half of all patients following a Kasai were at high risk for early progressive liver disease. TB ≥ 2.0 is a useful indicator of high risk.

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Adrenal Insufficiency due to Fluticasone in Eosinophilic Esophagitis

Posted on March 17, 2016 by gutsandgrowth

A recent study (MC Golekoh et al. J Pediatr 2016; 170: 240-5) shows that adrenal insufficiency developed in 10% of patients on chronic (>6 months) swallowed corticosteroid therapy for Eosinophilic Esophagitis (EoE).

Background: 58 patients with 67% receiving fluticasone and 33% receiving budesonide. Median age: 13.7, median fluticasone dose 1320 mcg/day, median treatment duration: 4 yrs. For budesonide, median dose was 1000 mcg/day and median age 10.7 yrs.

Key findings with low-dose ACTH stimulation:

Abnormal peak cortisol (≤ 20 mcg/dL) present in 15% and adrenal insufficiency (< 18 mcg/dL) (n=6) noted in 10%
Only patients receiving >440 mcg/day of fluticasone had adrenal insufficiency
No patients taking budesonide had an abnormal cortisol level

Commentary:

Higher doses of fluticasone, particularly early in treatment, has been shown to have an improved inflammatory response. However, as with asthma therapy, higher doses increase the risk of adrenal insufficiency.
Adrenal insufficiency can be asymptomatic but pose a risk for life-threatening adrenal crisis.
Strengths of study: Fairly large cohort, endoscopic/pathologic reports available, and ACTH stimulation testing which has better sensitivity than random cortisol.
Limitations: Lower number of patients receiving budesonide, particularly at a higher dose. No indication of adherence.

My take: If higher doses of fluticasone are needed for prolonged period, consider screening (endocrinology consultation) for adrenal insufficiency.

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CDC Guideline for Prescribing Opioids for Chronic Pain

Posted on March 16, 2016 by gutsandgrowth

Full Text: CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016

D Dowell et al. JAMA. Published online March 15, 2016. doi:10.1001/jama.2016.1464 .

Excerpts:

No evidence shows a long-term benefit of opioids in pain and function vs no opioids for chronic pain with outcomes examined at least 1 year later (with most placebo-controlled randomized clinical trials ≤6 weeks in duration).
Extensive evidence shows the possible harms of opioids (including opioid use disorder, overdose, and motor vehicle injury).
Extensive evidence suggests some benefits of nonpharmacologic and nonopioid pharmacologic therapy, with less harm.

CDC: “We know of no other medication routinely used for a nonfatal condition that kills patients so frequently,”

1st Six Recommendations (12 total)

1. Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient. If opioids are used, they should be combined with nonpharmacologic therapy and nonopioid pharmacologic therapy, as appropriate. (Recommendation category: A; evidence type: 3)

2. Before starting opioid therapy for chronic pain, clinicians should establish treatment goals with all patients, including realistic goals for pain and function, and consider how opioid therapy will be discontinued if benefits do not outweigh risks. Clinicians should continue opioid therapy only if there is clinically meaningful improvement in pain and function that outweighs risks to patient safety. (Recommendation category: A; evidence type: 4)

3. Before starting and periodically during opioid therapy, clinicians should discuss with patients known risks and realistic benefits of opioid therapy and patient and clinician responsibilities for managing therapy. (Recommendation category: A; evidence type: 3)

4. When starting opioid therapy for chronic pain, clinicians should prescribe immediate-release opioids instead of extended-release/long-acting (ER/LA) opioids. (Recommendation category: A; evidence type: 4)

5. When opioids are started, clinicians should prescribe the lowest effective dosage. (Recommendation category: A; evidence type: 3)

6. Long-term opioid use often begins with treatment of acute pain. When opioids are used for acute pain, clinicians should prescribe the lowest effective dose of immediate-release opioids and should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids. Three days or less will often be sufficient; more than 7 days will rarely be needed. (Recommendation category: A; evidence type: 4)

Other points:

Avoid concurrent benzodiazepines
Review state prescription drug monitoring program to look for dangerous combination therapies and prior opiod dosing
Consider risk mitigation strategies (eg. naloxone)
Suggests urine screening at start to screen for illicit substance abuse which increases risk

USAToday’s review of these guidelines: CDC issues new guideline on opiods

Bottomline: This report is very important for those who prescribe opiods for chronic pain.

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