Why Do Canadians with Cystic Fibrosis Live Longer than Patients in U.S.?

Posted on by

NY Times Summarizes the reasons why Canadians with Cystic Fibrosis Live Longer: Link:  Canadians With Cystic Fibrosis Live 10 Years Longer Than Americans With the Disease

Cystic fibrosis is an inherited disease that causes recurrent lung infections and other problems. The average lifespan for an American with the illness is 37 years. In Canada, it is 49.

Researchers studied records of 5,941 Canadian and 45,448 American cystic fibrosis patients between 1990 and 2013. After controlling for severity of disease, age and other factors, they found that overall death rates were 34 percent lower in Canada than in the United States.

There was no difference in death rates between Canadians and Americans with private health insurance. But Canada provides universal health care coverage under a single-payer system, so every Canadian has some kind of health insurance. The Canadian death rate was 44 percent lower than that of Americans on Medicaid or Medicare, and 77 percent lower than Americans without insurance.

 AL Stephenson et al.  Ann Intern Med. 2017. DOI: 10.7326/M16-0858

Abstract

Background:In 2011, the median age of survival of patients with cystic fibrosis reported in the United States was 36.8 years, compared with 48.5 years in Canada. Direct comparison of survival estimates between national registries is challenging because of inherent differences in methodologies used, data processing techniques, and ascertainment bias.
Objective:To use a standardized approach to calculate cystic fibrosis survival estimates and to explore differences between Canada and the United States.
Design:Population-based study.
Setting:42 Canadian cystic fibrosis clinics and 110 U.S. cystic fibrosis care centers.
Patients:Patients followed in the Canadian Cystic Fibrosis Registry (CCFR) and U.S. Cystic Fibrosis Foundation Patient Registry (CFFPR) between 1990 and 2013.
Measurements:Cox proportional hazards models were used to compare survival between patients followed in the CCFR (n = 5941) and those in the CFFPR (n = 45 448). Multivariable models were used to adjust for factors known to be associated with survival.
Results:Median age of survival in patients with cystic fibrosis increased in both countries between 1990 and 2013; however, in 1995 and 2005, survival in Canada increased at a faster rate than in the United States (P < 0.001). On the basis of contemporary data from 2009 to 2013, the median age of survival in Canada was 10 years greater than in the United States (50.9 vs. 40.6 years, respectively). The adjusted risk for death was 34% lower in Canada than the United States (hazard ratio, 0.66 [95% CI, 0.54 to 0.81]). A greater proportion of patients in Canada received transplants (10.3% vs. 6.5%, respectively [standardized difference, 13.7]). Differences in survival between U.S. and Canadian patients varied according to U.S. patients’ insurance status.
Limitation:Ascertainment bias due to missing data or nonrandom loss to follow-up might affect the results.
Conclusion:Differences in cystic fibrosis survival between Canada and the United States persisted after adjustment for risk factors associated with survival, except for private-insurance status among U.S. patients. Differential access to transplantation, increased posttransplant survival, and differences in health care systems may, in part, explain the Canadian survival advantage.
Primary Funding Source:U.S. Cystic Fibrosis Foundation.

Sainte-Chapelle, Paris

Colon Cancer at Younger Ages

Posted on by

From USA Today: Colon and rectal cancers surge in millennials and GenX

An excerpt:

Someone born in 1990 has double the risk of early colon cancer and quadruple the risk of early rectal cancer as someone born in 1950…

Most of the nation’s 135,000 annual cases and 50,000 deaths related to colon and rectal cancer still occur among people over age 55. But the share of cases involving younger adults has risen to 29% for rectal cancer and 17% for colon cancer, the study showed. About 11,000 people in their 40s and 4,000 under 40 were diagnosed in 2013…

Known risk factors for colon and rectal cancer include obesity, inactivity and diets high in red and processed meat and low fruits, vegetables and whole grains.

screenshot-163

March 2017 Briefs

Posted on by

MC Montana, AS Evers. J Pediatr 2017; 181: 279-84. This commentary reviewed recent studies regarding anesthetic neurotoxicity. “Two recently published human studies suggest a lack of harm in otherwise-healthy children following a short duration anesthetic (approximately 1 hour)” References: Lancet 2016; 387: 239-50 & JAMA 2016; 315: 2312-20.

Related posts:

NR Santucci et al. JPGN 2017; 64: 186-93.  This systematic review selected 31 studies (out of 916 citations) and found there is no consensus concerning diagnostic criteria for biliary dyskinesia and the data supporting the concept of biliary dyskinesia in children is weak.  The uncontrolled studies were generally observational, retrospective designs with relatively small numbers.

Related posts

I Youngster et al. J Pediatr 2017; 182: 239-44.  This study examined large prescription databases (more than 74 million person years) and identified wide discrepancy in antibiotic use among the six different countries.  For example, among children less than 2 years of age, South Korea had the highest rate of antimicrobial use, with 3.41 prescribed courses per child-year; in contrast, the rates were 1.4 in Italy, 1.5 in Spain, 1.1 in the U.S., 1.0 in Germany, and 0.5 in Norway.

A Srivastavai et al. JPGN 2017; 64: 194-9. In this retrospective study with 262 children with liver disease-related ascites, the authors found spontaneous bacterial peritonitis (or culture-negattive neurocytic ascites) in 28.6%. Half of these patients were asymptomatic.  SBP/CNNA was defined by having a polymorphonuclear leukocyte count of >250 cells/mm3.  There was a 24% one-year mortality rate for those who had SBP/CNNA.

MR Narkewicz et al. JPGN 2017; 64: 210-7. Using data from the pediatric acute liver failure group, the researchers identified a high rate of autoantibodies (28%) among 986 pediatric subjects with acute liver failure. The presence of autoantibodies was not significantly associate with 21-day outcomes and steroid treatment was not associated with survival; in fact, those without a known diagnosis of autoimmune hepatitis, had a higher risk of death with steroid therapy. In the setting of acute liver failure, autoantibody positivity does not obviate the need for a complete diagnostic workup.

A Lauterio et al. Liver Transplantation 2017; 23: 184-93.  Italian review of living donor safety found that major complications occurred in 12.6% (31 or 246)  but there were no mortalities. 5 (2%) required reoperation.

 

from Twitter's 'This Week in Church Signs' feed

from Twitter’s ‘This Week in Church Signs’ feed

Celiac Diseaase and Diabetes

Posted on by

A recent review (B Weiss, O Pinahs-Hamiel. JPGN 2017; 64: 175-79) of the medical literature describes the various recommendations regarding celiac disease (CD) and type 1 diabetes mellitus (T1DM).

Key points:

  • Two-thirds of patients with T1DM and CD are asymptomatic for CD at diagnosis
  • Many children with T1DM and with positive CD serology may normalize the serology spontaneously.   In one study with 446 children with T1DM who were screened for CD, 38 had persistently abnormal serology whereas 27 had fluctuations in CD serology.  In another study with 738 children, of 48 patients with positive CD serology, normalization was evident in 35% at 1 year.

The authors review recommendations for CD screening.  Several guidelines have recommended soon after diagnosis (especially if >2 years of age).

screenshot-149

Their figure 1 algorithm provides guidance on evaluation.  In those patients with T1DM and positive CD serology, if they are asymptomatic, assuring that serology is persistently elevated may be worthwhile before proceeding with small bowel biopsy.  In those who initially test negative for serology, there may be a role for HLA testing and/or periodic screening every few years.

Related editorial on recent article: Celiac Disease, Gut-Brain Axis, and Behavior: Cause, Consequence or Merely Epiphenomenon (A Fasano)  Thanks to KT Park for this reference.  Excerpt:

By assessing the psychological functioning of infants enrolled in the Environmental Determinant of Diabetes in the Young trial and followed prospectively, the authors reported that 3.5-year-old children affected by celiac disease autoimmunity (CDA), defined as positive serology in children at risk, have increased reports of depression/anxiety, aggressive behavior, and sleep disturbances. Interestingly, these symptoms were significantly greater in the 66 children with CDA whose mothers were unaware of the diagnosis compared with the 440 children with CDA whose mothers were aware of the diagnosis and the 3651 children without CDA, decreasing the chance that the reported behaviors were biased by families’ subjective assessment…Prospective studies such as that reported by Smith et al may be a key approach to shedding light on how intestinal factors can influence human behavior and to identifying possible targets to ameliorate psychological symptoms caused by inappropriate gut-brain cross-talk.

Reference article: Smith L, et al.. Psychological manifestation of celiac disease autoimmunity in young children. Pediatrics. 2017;139(3):e20162848

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Bone Health and Intestinal Failure

Posted on by

Link: Bone Health of Children with Intestinal Failure (Thanks to Kipp Ellsworth for this reference) E Neelis et al. DOI: http://dx.doi.org/10.1016/j.clnu.2017.02.014

From Abstract:

Methods

A retrospective study was performed including all children with IF between 2000 and 2015 who underwent a DXA measurement and/or a hand radiograph. Z-scores of BMD total body (BMD TB) and lumbar spine (BMD LS), bone mineral apparent density (BMAD) and bone health index (BHI) were collected. A low BMD and low BHI were defined as a Z-score ≤ -2. DXA and DXR results were compared for cases in which a DXA and hand radiograph were performed within a 6 months’ interval.

Results

Forty-six children were included. Overall, 24.3% of the children had a low BMD at the first DXA at a median age of 6 years; correction for growth failure (n=6)) reduced this to 16.2%. Fifty percent had a low BHI at the first hand radiograph. Median DXA and BHI Z-scores were significantly lower than reference scores. Age, duration of PN and surgical IF were related to lower Z-scores at the first DXA. Paired DXA and DXR results (n=18) were compared, resulting in a Cohen’s kappa of 0.746 (‘substantial’) for BMD TB. Spearman’s correlation coefficient for BHI and BMD TB Z-scores was 0.856 (p<0.001). Hand radiography had a sensitivity of 90% and specificity of 86% (BMD TB).

Conclusions

Up to 50% of the children had a low BMD. Children with IF have a significantly poorer bone health than the reference population, also after weaning off PN. Bone health assessment by DXA and DXR showed good agreement, especially for Z-scores ≤ -2. DXR assessment using BoneXpert software seems to be feasible for monitoring of bone health in children with IF.

screenshot-148

Rising Rates of Pediatric Fatty Liver

Posted on by

The alarming rates of pediatric nonalcoholic fatty liver disease are summarized in a recent Lancet Blog (Thanks to John Pohl for this link).  Seven million children in U.S. have fatty liver disease.

Link: An alarming trend in fatty livers (in children)

An excerpt:

The rate of NAFLD among US children has tripled over the last twenty to thirty years, rising from 3-4 percent to 10-11 percent, according to Dr. Naim Alkhouri, Director of the Metabolic Liver Center at the Texas Liver Institute in San Antonio…

Lifestyle changes, such as better nutrition and increased exercise, are currently the best-known way of mitigating and possibly reversing its effects…

Some 35-50 percent of obese children have NAFLD, and 20 percent of children with NAFLD have the advanced form of NASH. Also, 10-15 percent of children with NAFLD are in a predicament that could be described as “pre-cirrhosis.”

“Though most cases of juvenile NAFLD are caused by excess weight and associated insulin resistance, “up to 7% of non-overweight or obese children may have NAFLD,” according to a new study that Alkhouri and others will present at the upcoming International Liver Congress, held in Amsterdam this April.

Related blog posts:

Chattahoochee near Azalea Drive

Chattahoochee near Azalea Drive

What’s at Stake with “Repeal and Replace”

Posted on by

Full Link from NEJM: The Mirage of Reform — Republicans’ Struggle to Dismantle Obamacare

Here’s an excerpt:

The [AHCA] bill distinguishes itself from the ACA largely by its commitment to regressive redistribution: it would give wealthier Americans more money (mainly through sizable tax cuts) while reducing government support to help low-income Americans afford insurance. Relative to the ACA, premium subsidies for the uninsured would decrease substantially, on average by 40% in 2020 and reaching 50% by 2026.1 Those cuts would fall heavily on lower-income people, with middle- and upper-income Americans receiving higher subsidies.1,3 The ACA’s subsidies to assist low-income persons with deductibles and copayments would be eliminated altogether. By 2026, for a person earning $26,500 a year and buying individual coverage, insurance plans’ actuarial value — which measures the share of costs that plans pay for covered services — would fall from 87% under the ACA to 65% under the GOP plan…

In addition to unified Democratic and significant Republican opposition in Congress and among governors, key stakeholders — including the American Medical Association, the American Hospital Association, and the seniors advocacy group AARP — oppose the bill. Furthermore, as its potential demise draws nearer, the popularity of the ACA, now part of the status quo, is growing. In the Republican imagination, Obamacare has been a disaster. The GOP’s problem is that in reality Obamacare has substantially expanded health coverage, with 20 million Americans gaining insurance. Rolling back the ACA means making insurance less affordable for low-income Americans, increasing the uninsured population, and taking vast funds away from states and medical providers. The GOP health plan neither fully repeals the ACA nor provides a compelling replacement. Instead, in my opinion, it offers only a mirage of reform.

Another analysis indicates significantly higher deductibles are likely under the GOP plan:

Link: Why dedcuctibles would increase under the GOP health plan

Infliximab Not Associated with Malignancy

Posted on by

JS Hyams et al. Gastroenterology http://dx.doi.org/10.1053/j.gastro.2017.02.004

Using the DEVELOP registry, a prospective study showed no increased risk of malignancy among 5766 pediatric participants with inflammatory bowel disease.

Link: Full Abstract

Immunosuppressive therapy for inflammatory bowel disease (IBD) in pediatric patients is thought to increase risk of malignancy and lymphoproliferative disorders, including hemophagocytic lymphohistiocytosis (HLH). We compared unadjusted incidence rates and of malignancy and HLH in pediatric patients with IBD exposed to infliximab compared with patients not exposed to biologics and calculated standardized incidence ratios (SIRs).

Methods

We collected and analyzed data from 5766 participants in a prospective study of long-term outcomes of pediatric patients with IBD (NCT00606346), from 2007 through 30 June 2016. Patients were 17 years old or younger and had Crohn’s disease, ulcerative colitis, or IBD unclassified with 24,543.0 patient-years of follow-up. We estimated incidence rates for malignancy and HLH as events/1000 patient-years of follow-up. We calculated age-, sex-, and race-adjusted SIRs, with 95% CIs, using the Surveillance, Epidemiology, and End Results Program (SEER) database.

Results

Thirteen of the 15 patients who developed a malignancy and all 5 of the patients who developed HLH had been exposed to thiopurine; 10 patients with malignancy patients had also been exposed to a biologic agent. Unadjusted incidence rates showed no increased risk of malignancy (0.46/1000 patient-years) or HLH (0.0/1000 patient-years) in patients exposed to infliximab as the only biologic vs those unexposed to biologics (malignancy: 1.12/1000 patient-years; HLH: 0.56/1000 patient-years). SIRs did not demonstrate an increased risk of malignancy among patients exposed to infliximab (SIR; 1.69; 95% CI, 0.46–4.32) vs patients not exposed to a biologic agent (SIR, 2.17; 95% CI, 0.59–5.56), even when patients were stratified by thiopurine exposure.

Conclusions

In determination of age-, sex- and race-adjusted SIRs using data from a large clinical trial and the SEER database, we found that infliximab exposure did not associate with increased risk of malignancy or HLH in pediatric patients with IBD. Thiopurine exposure is an important precedent event for the development of malignancy or HLH in pediatric patients with IBD.

Related blog posts:

 

Turning Liquid into Gold: A Pharmaceutical Rumpelstiltskin Story

Posted on by

A recent letter to the editor (LA Probst, TR Welch. NEJM 2017; 376: 795-6) provides a sad tale of how well-intended legislation to promote safety and efficacy of pediatric liquid medications has led to both an increased number of liquid formulations approved by the FDA but with a much higher cost than previous extemporaneously compounded formulations.

The liquid version of lisinopril is priced 775 times the cost of the equivalent tablet.  Other medications with high liquid to tablet cost ratios include enalapril (21 times), indomethacin (49 times), glycopyrrolate (14 times), and pyridostigmine (11 times).

The authors note that there are additional costs for developing/manufacturing these liquid formulations.

My take (borrowed from the authors): “there must be a better way to support the costs of developing the drug formulations that many children and some severely impaired adults desperately need.”

Related blog posts:

Chattahoochee near Azalea drive

Chattahoochee near Azalea drive