Monthly Archives: September 2015

5000% Increase for Well-Established Drug

Posted on by

There is yet another outrageous example of a pharmaceutical company jacking up the price of a medication, without any added innovation, due to monopolizing its production.

From USA Today: Company hikes price 5000%.  Here’s an excerpt:

Turing Pharmaceuticals of New York raised the price of Daraprim from $13.50 per pill to $750 per pill last month, shortly after purchasing the rights to the drug from Impax Laboratories. Turing has exclusive rights to market Daraprim (pyrimethamine), on the market since 1953.

Daraprim fights toxoplasmosis, the second most common food-borne disease, which can easily infect people whose immune systems have been weakened by AIDS, chemotherapy or even pregnancy, according to the Centers for Disease Control.,,,

About 60 million people in the United States may carry the Toxoplasma parasite, according to the CDC. It comes from eating under-cooked meat, cooking with contaminated knives and boards, drinking unclean water and contact with infected cat feces.

Mothers can also pass it to their children during pregnancy and organ transplant patients can get it through an infected donor.

My take: This type of excessive drug cost increase is why critics demand additional regulation be placed over the entire pharmaceutical industry; it can occur only in a system which indirectly shares the cost across the entire system by having insurance companies foot most of the bill.  In my view, this increase in cost is equivalent to the water company jacking up your water bill 5000% –how would you feel about that?

Related posts:

Overdiagnosis of Clostridium difficile with PCR Assays

Posted on by

A recent study (JAMA Intern Med. Published online September 08, 2015. doi:10.1001/jamainternmed.2015.4114) indicates that use of PCR assays to detect C diff results in overdiagnosis and overtreatment.  Perhaps, a more selective approach to using C diff PCR assay is needed and returning to use of toxin immunoassays is worthwhile.  

 

ABSTRACT:

Importance  Clostridium difficile is a major cause of health care–associated infection, but disagreement between diagnostic tests is an ongoing barrier to clinical decision-making and public health reporting. Molecular tests are increasingly used to diagnose C difficile infection (CDI), but many molecular test-positive patients lack toxins that historically defined disease, making it unclear if they need treatment.

Objective  To determine the natural history and need for treatment of patients who are toxin immunoassay negative and polymerase chain reaction (PCR) positive (Tox−/PCR+) for CDI.

Design, Setting, and Participants  Prospective observational cohort study at a single academic medical center among 1416 hospitalized adults tested for C difficile toxins 72 hours or longer after admission between December 1, 2010, and October 20, 2012. The analysis was conducted in stages with revisions from April 27, 2013, to January 13, 2015.

Main Outcomes and Measures  Patients undergoing C difficile testing were grouped by US Food and Drug Administration–approved toxin and PCR tests as Tox+/PCR+, Tox−/PCR+, or Tox−/PCR−. Toxin results were reported clinically. Polymerase chain reaction results were not reported. The main study outcomes were duration of diarrhea during up to 14 days of treatment, rate of CDI-related complications (ie, colectomy, megacolon, or intensive care unit care) and CDI-related death within 30 days.

Results  Twenty-one percent (293 of 1416) of hospitalized adults tested for C difficile were positive by PCR, but 44.7% (131 of 293) had toxins detected by the clinical toxin test. At baseline, Tox−/PCR+ patients had lower C difficile bacterial load and less antibiotic exposure, fecal inflammation, and diarrhea than Tox+/PCR+ patients (P < .001 for all). The median duration of diarrhea was shorter in Tox−/PCR+ patients (2 days; interquartile range, 1-4 days) than in Tox+/PCR+ patients (3 days; interquartile range, 1-6 days) (P = .003) and was similar to that in Tox−/PCR− patients (2 days; interquartile range, 1-3 days), despite minimal empirical treatment of Tox−/PCR+ patients. No CDI-related complications occurred in Tox−/PCR+ patients vs 10 complications in Tox+/PCR+ patients (0% vs 7.6%, P < .001). One Tox−/PCR+ patient had recurrent CDI as a contributing factor to death within 30 days vs 11 CDI-related deaths in Tox+/PCR+ patients (0.6% vs 8.4%, P = .001).

Conclusions and Relevance  Among hospitalized adults with suspected CDI, virtually all CDI-related complications and deaths occurred in patients with positive toxin immunoassay test results. Patients with a positive molecular test result and a negative toxin immunoassay test result had outcomes that were comparable to patients without C difficile by either method. Exclusive reliance on molecular tests for CDI diagnosis without tests for toxins or host response is likely to result in overdiagnosis, overtreatment, and increased health care costs.

Related blog posts:

“Not Up For Debate: The Science Behind Vaccination”

Posted on by

Wednesday’s well publicized debate unfortunately discussed vaccination.  Perhaps it is not surprising that a businessman/entertainer, Donald Trump, reiterated misinformation.  Yet, the two former physicians (Ben Carson and Rand Paul) on the stage also provided misleading information.  A good write-up of this issue from the NY Times: Not Up for Debate: The Science Behind Vaccination

Here’s an excerpt:

Here are the facts:

  • Vaccines aren’t linked to autism.
  • The number of vaccines children receive is not more concerning than it used to be.
  • Delaying their administration provides no benefit, while leaving children at risk.
  • All the childhood vaccines are important.

Antivirals Reduce Vertical Transmission of Hepatitis B

Posted on by
Chelsea Market, NYC

Chelsea Market, NYC

The latest study that shows antivirals interrupt hepatitis B viral (HBV) transmission from mother-to-infant: H-L Chen et al. Hepatology 2015; 62: 375-86.

In this open-label, non-randomized controlled study from Taiwan, the researchers recruited women to receive tenofovir (TDF) at a dose of 300 mg once a day (n=62), initiated from gestational age 30-32 weeks until 1 month following delivery, and compared them to a control group (n=56).  There were high levels of viremia with HBV DNA ≥7.5 log10 IU/mL. All infants received HBV vaccination and HBIG within 24 hours of birth.

Key findings:

  • Infant transmission of HBV was reduced: at 6 months of age, infant HBsAg positivity was 1.54% versus 10.71%, P=0.0481).  At delivery, HBV DNA positivity was noted in 6.15% compared with 31.48% of the control group.
  • Maternal ALT was improved in the TDF group. ALT elevation more than two times the upper limit of normal for ≥3 months occurred in 3.23% compared with 14.29% of controls.
  • Adverse effects: only mild to moderate (self-limited) gastrointestinal and skin symptoms were noted. No fetal abnormalities were identified.

Bottomline: Antivirals, including both tenofovir and telbivudine, reduce vertical HBV transmission with a favorable safety profile.  The use of antivirals is complementary to standard prevention which consists of providing Hepatitis B immune globulin and Hepatitis B vaccine to infants of HBV-infected pregnant women within 12 hours of birth.

Related blog posts:

Celiac Update September 2015

Posted on by

A useful review (CP Kelly et al. Gastroenterol 2015; 148: 1175-86) summarizes the ‘state of the art” information regarding celiac disease presentation and management. The review notes that some expert organization consensus state that intestinal biopsy is mandatory whereas some do not under certain conditions.

According to ESPGHAN, if anti-TTG >10-fold elevated, anti-EMA positive in separate sample, and +HLA typing, then a biopsy may not be required.  For the WGO (World Gastroenterologic Organization), the exception focuses on available local resources.

The article recommends the following for monitoring:

  • Clinical evaluation -annually or if recurrent symptoms
  • Serology & Nutritional evaluation -every 3-6 months until normal, then every 1-2 years.  Common nutrient deficiencies: iron, vitamin D, vitamin B12, folate, and zinc
  • Bone density -once within first 2 years.  (Some recommend checking after 1 year on gluten free diet)
  • Liver transaminase levels & Thyroid function tests -at diagnosis, then every 1-2 years.  Autoimmune thyroid disorders are “found in approximately 15-20% of adults with celiac disease”

A second retrospective indicates that ESPGHAN criteria for avoiding biopsy in children and adolescents with high titers for anti-TTG (>10-fold) along with positive EMA, and HLA-DQ2/DQ8.are reasonable.  Here’s the abstract:

Are ESPGHAN “Biopsy-Sparing” Guidelines for Celiac Disease also Suitable for Asymptomatic Patients?

CM Trovato, et al.The American Journal of Gastroenterology , (15 September 2015) | doi:10.1038/ajg.2015.285

OBJECTIVES:

In 2012, European Society of Pediatric Gastroenterology, Hepatology, and Nutrition published novel guidelines on celiac disease (CD) diagnosis. Symptomatic children with serum anti-transglutaminase (anti-tTG) antibody levels ≥10 times upper limit of normal (ULN) could avoid duodenal biopsies after positive HLA test and serum anti-endomysial antibodies (EMAs). So far, both asymptomatic and symptomatic patients with anti-tTG titer <10 times ULN should undergo upper endoscopy with duodenal biopsies to confirm diagnosis. The aim of this study was to assess the accuracy of serological tests to diagnose CD in asymptomatic patients.

METHODS:

We retrospectively reviewed data of 286 patients (age range: 10 months to 17 years) with CD diagnosis based on elevated titer of anti-tTG, EMA positivity, and histology. All patients were distinguished between symptomatic and asymptomatic; histological lesions were graded according to the Marsh–Oberhuber (MO) criteria. Fisher exact test was applied to analyze both groups in terms of diagnostic reliability of serological markers.

RESULTS:

A total of 196 patients (68.53%) had anti-tTG titers ≥10 times ULN. Among them, a group of 156 patients (79.59%) also had symptoms suggestive of CD (“high-titer” symptomatic); of these, 142 patients (91.02%) showed severe lesion degree (3a, 3b, 3c MO). Conversely, 40 out of 196 patients (20.40%) were asymptomatic (“high-titer” asymptomatic) and 37 patients (92.5%) of them showed severe lesion degree (3a, 3b, 3c MO). No difference in histological damage was found between “high-titer” symptomatic and “high-titer” asymptomatic children (Fisher exact test, P=1.000).

CONCLUSIONS:

If confirmed in large multicenter prospective studies, the “biopsy-sparing” protocol seems to be applicable to both symptomatic and asymptomatic patients with anti-tTG titer ≥10 times ULN, positive EMA, and HLA-DQ2/DQ8.

Related blog posts:

 

 

Celiac Disease: “Ten Things That Every Gastroenterologist Should Know”

Posted on by

Turns out that a recent review (AS Oxentenko, JA Murray. Clin Gastroenterol Hepatol 2015; 13: 1396-1404) is a succinct summary on celiac disease with questions focused on diagnosis, endoscopy, genetics/HLA typing, at risk groups, management, adherence, non responsive celiac patient, and refractory patients.  Most of these topics have been addressed previously on this blog.

However, here are a few pointers:

  • “Histologic improvement is slow in adults…Mucosal recovery, defined by a villous:crypt ratio of 3:1, was present in 34% at 2 years and 66% at 5 years, with healing complete in 90% by 9 years.”
  • “Mucosal recovery is faster and more complete in children, with 95% recovery in 2 years and 100% recovery long-term in children following a GFD.”
  • With nonresponsive celiac disease, “defined as a lack of response to 6 months on a GFD or a recurrence of celiac-related features despite compliance,” the authors recommend reviewing serology and biopsies.  Other etiologies to consider include bacterial overgrowth, autoimmune enteropathy, tropical sprue, Crohn’s disease, combined variable immunodeficiency, collagenous sprue, and eosinophilic gastroenteritis.
  • For refractory celiac disease with ongoing villous atrophy, this “should prompt immunophenotyping and T-cell rearrangement studies” of duodenal biopsies.

Briefly noted: ET Jensen et al. Clin Gastroenterol Hepatol 2015; 13: 1426-31.  The authors examined 88,517 patients who had undergone both esophageal and duodenal biopsies.  “Odds of EoE (eosinophilic esophagitis) were 26% higher in patients with celiac disease than in patients without celiac disease” (adjusted odds ratio 1.26).

Related blog posts:

From the High Line, NYC

From the High Line, NYC

“The Solution to Drug Prices”

Posted on by

Worth a read: “The Solution to Drug Prices” by Eziel Emanuel

An excerpt:

WE’RE paying too much for prescription drugs….Despite representing about 1 percent of prescriptions in 2014, these types of high-cost drugs accounted for some 32 percent of all spending on pharmaceuticals….

Almost all developed countries… making drugs available at fixed prices …Drug companies would immediately raise two objections: the high risks associated with drug development and, related, the high cost of research and development. But both of these arguments are fatuous…

Also, as outrageous as they are, prices are not the real issue. Value is. What really frustrates people are expensive drugs that do not provide a cure. For instance, Opdivo adds an average of 3.2 months of life to lung cancer patients and costs $150,000 per year for treatment…

Everyone, including drug company executives, believes that high prices cannot continue. Indeed, that is one reason that companies are trying to maximize profits while they can. We must come up with a comprehensive solution now.

Parenteral Nutrition and False Positive Newborn Screens, Plus One

Posted on by

Briefly noted:

“Stopping Parenteral Nutrition for 3 Hours Reduces False Positives in Newborn Screening” T Tim-Aroon et al. J Pediatr 2015; 167: 312-6. By stopping parenteral nutrition (PN), the authors reduced false-positive results for amino acid disorders among newborn screenings. In patients receiving PN, holding PN (and using IVFs) was associated with a false-positive rate of 2/65 compared with 29/245 who continued PN (3.1% vs. 11.8%; P=.037)

“Age at Weaning and Infant Growth: Primary Analysis and Systemic Review” B Vail et al. J Pediatr 2015; 167: 317-24. UK prospective study with n=571 singletons along with systemic review which identified two trials. Conclusion: “In high-income countries, weaning between 3 and 6 months appears to have a neutral effect on infant growth.  Inverse associations are likely related to reverse causality.”

 

 

Just Saying…Vaccines Don’t Trigger Inflammatory Bowel Disease

Posted on by

The other day I was having a fun discussion on words that we may choose before providing information that others might not like.  Some examples:

  • “No offense but”…
  • “Don’t take this the wrong way”…
  • “Just saying”…

A recent report (GP de Chambrun et al. Clin Gastroenterol Hepatol 2015; 13: 1405-15) debunks claims that vaccines increase the risk of inflammatory bowel disease (IBD).  A report by Thompson NP et al (Lancet 1995; 345: 1071-74) suggested that measles vaccination could increase risk of IBD.  In the current study, the researchers examined 11 previous studies for review and meta-analysis.  Vaccines included: BCG, DPT, smallpox, poliomyelitis, pertussis, H1N1,measles, mumps, rubella, and combined MMR.  This study included 2399 patients with IBD and 33,747 controls. Bottomline: “Results of this meta-analysis show no evidence supporting an association between childhood immunization or H1N1 vaccination in adults and risk of developing IBD.” With regard to the measles vaccine in particular, the relative risk was 1.33 (CI 0.31 -5.80) in cohort studies and the relative risk was 0.85 (CI 0.60 -1.20) in case-control studies.

What types of words do you hear people use before saying something someone is not going to like?

Related posts:

Desperate Measures in Refractory IBD

Posted on by

The often cited, ‘desperate times call for desperate measures,’ resonates in the setting of refractory inflammatory bowel disease (IBD).  [Of course, this saying could be used to justify about anything you want to do.]  For IBD, two recent studies point out potential remedies:

  • SA Merkley, et al. Inflamm Bowel Dis 2015; 21: 1854-59.
  • M Lazzerini, et al. Inflamm Bowel Dis 2015; 21: 1739-49, with editorial by A Bousvaros (1750-51)

In the first study, the authors retrospectively analyzed date from 24 IBD patients who were treated with intravenous immunoglobulin (IVIG) at a dose of 0.4 g/kg/day for 3 days, then 0.4 g/kg once a month. Key findings: 16 (67%) had a response and 3 (12.5%) obtained remission. Measures of improvement included CRP, ESR, Simple Endoscopic Score for Crohn’s disease, and the Harvery-Bradshaw Index. The researchers speculate that IVIG has anti-inflammatory and immunomodulator effects.  In addition, they note that IVIG can be given with concurrent infections.

In the second study, the authors studied thalidomide(1.5-2.5 mg/kg/day) in a double-blind, placebo-controlled randomized pediatric clinical trial in children with refractory active ulcerative colitis. Key findings: at week 8, clinical remission was achieved in 10/12 (83%) of thalidomide arm compared with 2/11 (19%) of control patients.  Then, among control patients who were switched, 8 of 11 (72%) reached remission as well. Peripheral neuropathy and amenorrhea were reported adverse effects. In the accompanying editorial, Dr. Bousvaros notes that there has been some data to suggest thalidomide efficacy in ulcerative colitis since 1979.  However, due to widespread bad publicity related to thalidomide-induced teratogenicity (eg. phocomelia) and side effects including neuropathy, it has not been used with much frequency. He notes that this study, as well, requires replication and speculates that “the primary focus on drug development will focus on newer small molecules and biologics, and this potentially useful medication may be left on the sidelines.” It is worth noting that the authors response (pg 1752) to this editorial was that the stigma of thalidomide is unwarranted and that teratogenicity can be avoided. “No case was observed out of 124,000 patients enrolled in the thalidomide distribution risk management program for more than 6 years.”

Bottomline: Both thalidomide and IVIG may be beneficial to desperate patients (and desperate doctors).  While small trials appear promising, larger trials are needed.  Don’t hold your breath waiting … will they ever happen?

Related blog posts: