This prospective study (n=80) expands on previous observations regarding the use of a transanal irrigation device for neurogenic bowel management.
Key points:
The neurogenic bowel dysfunction (NBD) score improved at both time points (<6 months, >6 months) by 14 and 13 points respectively. 94% and 98% had improved NBD score at time 1 and time 2 respectively
Patient satisfaction was high, though 8 patients discontinued device early on due to either discomfort or poor results
NBD score can used to monitor treatment effectiveness
This article describes a retrospective review of seven patients with a dual diagnosis of inflammatory bowel disease (IBD) and chronic recurrent multifocal osteomyelitis (CRMO). In their cohort 4 of 6 were receiving anti-TNF therapy at the time of CRMO diagnosis. Misleading statements from this article:
The triad of IBD, CRMO and psoriasis has not been reported previously to their knowledge
“It seems unlikely that anti-TNF-alpha therapy would promote its [CRMO] development”
In JPGN Reports (not available on pubmed), Cordesse et al (JPGN Reports; November 2020 – Volume 1 – Issue 2 – p e007) identified the association of IBD, CRMO and psoriasis; in addition, they identified a paradoxical reaction to anti-TNF-alpha therapy; in this case series of three patients, anti-TNF-alpha therapy triggered CRMO and stopping anti-TNF-alpha therapy led to resolution of CRMO in two of the cases.
In a response to a letter to the editor (Hochman JA. JPGN 2022; DOI: 10.1097/MPG.0000000000003407. Faulty Information Regarding CRMO and IBD), Dushnicky et al (DOI: 10.1097/MPG.0000000000003433) note that JPGN Reports is not available on Pubmed; however, the articles that have described this association are near the top of a google search if one looks for “IBD, CRMO and Psoriasis.” Interestingly, in their response to the letter to the editor, the authors did not amend their claim that anti-TNF therapy is unlikely to promote CRMO despite being furnished with information showing that it can. In my view, the situation with CRMO is similar to psoriasis which can be treated with anti-TNF therapy and can paradoxically be caused by anti-TNF agents as well.
My take:
CRMO is important to recognize due to its association with IBD and to realize that antibiotics are not an effective treatment.
Anti-TNF-alpha agents can cause CRMO in some patients.
In 2022, a web browser search (eg Google), in addition to Pubmed, is probably worthwhile when claiming that this is the first case of xyz ‘to our knowledge.’
This retrospective cohort study followed 17.6 million adult residents of California for up to 12 years.
Key findings:
Overall rates of homicide were more than twice as high among cohabitants of handgun owners than among cohabitants of nonowners (adjusted hazard ratio, 2.33).
These elevated rates were driven largely by higher rates of homicide by firearm (adjusted hazard ratio, 2.83).
Among homicides occurring at home, cohabitants of gun owners had sevenfold higher rates of being fatally shot by a spouse or intimate partner (adjusted hazard ratio, 7.16); 84% of these victims were female.
My take: Gun ownership increases the likelihood of firearm-related deaths.
No Exaggeration: Too Many Children Are Dying in the U.S. “The sad fact is that a child or adolescent in the United States is 57% more likely to die by the age of 19 years than those in other wealthy nations.” This is due mainly to more deaths from MVAs and from gun violence.
“There is no level of drinking that does not confer heart disease risk. The risk is small if people have an average of seven drinks a week when compared with none. But it increases quickly as the level of alcohol consumption rises”
“The study, which may help resolve medical disputes over the effects of alcohol on the heart, involved sophisticated analyses of the genes and medical data of nearly 400,000 people who participate in the U.K. Biobank”
“Some researchers have reported that drinking modestly protects the heart because moderate drinkers as a group have less heart disease than those who drink heavily or those who abstain. Dr. Aragam and his colleagues also saw that effect. But the reason, they report, is not that alcohol protects the heart. It is that light to moderate drinkers — those who consume up to 14 drinks a week — tend to have other characteristics that decrease their risk, like smoking less, exercising more and weighing less than those who drink more heavily and those who do not drink.“
“Many earlier studies of alcohol consumption and heart health were observational, meaning the subjects were followed over time to see if the amount of drinking was linked to heart health. Such studies are only able to find correlation but not causation, researchers say. But the Biobank study’s use of Mendelian randomization is more suggestive of causality, and so its results might carry more weight.”
My take: Light alcohol consumption is NOT beneficial for your heart.
In this pilot study, 12 individuals completed a web-based curriculum for VCE proficiency.
Key finding:
Participants showed significant improvement in knowledge (P = 0.041) and photo recognition posttests (P = 0.015). All participants who completed the curriculum found it helpful and reported that they would recommend it to their colleagues
The discussion notes that “Studies have demonstrated that competence with VCE develops in an endoscopist after reading 10–15 VCE studies (6,10). There are some newer guidelines that suggest that this number may be higher…[and] it requires continuous practice. Pediatric gastroenterologists may feel their skills are not adequate when VCEs are not performed on a consistent basis at their institution”
Previous studies have shown an association between the early use of antibiotics and an increased risk of inflammatory bowel disease. A recent study examined all the children born in Denmark from 1995-2009 and followed them up to 2013 via a prospectively maintained database.
During a median 9.5 years (9.3 million total person-years), CD was diagnosed in 208 of 979,039 children.
Key findings:
Antibiotic use in the first year of life was associated with a higher risk of CD (adjusted hazard ratio, 1.4)…with the highest risk with ≥6 courses of antibiotics (adjusted hazard ratio, 4.1)
The cumulative risk of CD at the 11th birthday for children exposed to antibiotics in their first year of life was 0.16% compared to 0.11% for children unexposed to antibiotics in their first year of life.
My take: This study indicates that antibiotics (and/or serious infections) are associated with an increased the risk of pediatric Crohn’s disease but the absolute risk is very low. We still have a lot to learn about how environmental exposures, including diet, infections, antibiotics, and pollution, contribute to the increasing prevalence of inflammatory bowel disease.
It is well-recognized that genetic mutations that persist often confer some advantages. For example, sickle cell trait (but not disease) provides protection against malaria.
Methods: “The association between c.273_274delAG and phenotypes related to metabolic health was assessed in 2 cohorts of Greenlandic adults (n = 4922 and n = 1629). A sucrase-isomaltase knockout (Sis-KO) mouse model was used to further elucidate the findings”
Key findings:
Homozygous carriers of the variant had a markedly healthier metabolic profile than the remaining population, including lower body mass index ( –2.0 kg/m2; P = 3.1 × 10–5), body weight (–4.8 kg; P = 5.1 × 10–4), fat percentage (–3.3%; P = 3.7 × 10–4), fasting triglyceride (–0.27 mmol/L; P = 2.3 × 10–6), and remnant cholesterol (–0.11 mmol/L; P = 4.2 × 10–5).
The metabolic profile “was likely mediated partly by higher circulating levels of acetate observed in homozygous carriers” (0.056 mmol/L; P = 2.1 × 10–26), and partly by reduced sucrose uptake, but not lower caloric intake.
“These findings were verified in Sis-KO mice, which, compared with wild-type mice, were leaner on a sucrose-containing diet, despite similar caloric intake, had significantly higher plasma acetate levels in response to a sucrose gavage, and had lower plasma glucose level in response to a sucrose-tolerance test.”
My take: It should not be surprising that a genetic condition that results in limited sucrose intake would have health benefits. Perhaps correcting this condition will result in unexpected health issues similar to health issues that can develop in those with celiac disease after institution of a gluten-free diet (Gastroenterol 2013; 144: 912-17).
Background: “Proton pump inhibitors (PPIs) are among the most commonly used medications in the United States, if not the world. Observational studies have demonstrated that PPI use has increased over time and that 7%–15% of patients use these medications at any time, with the prevalence increasing to 40% for patients 70 years or older…In a large observational study examining ambulatory visits of PPI users, nearly two-thirds had no clear indication for PPI use.”
Some of the best practice advice:
Best Practice Advice 2 All patients taking a PPI should have a regular review of the ongoing indications for use and documentation of that indication. This review should be the responsibility of the patient’s primary care provider.
Best Practice Advice 3 Most patients with an indication for chronic PPI use who take twice-daily dosing should be considered for step down to once-daily PPI.
Best Practice Advice 4 Patients with complicated gastroesophageal reflux disease, such as those with a history of severe erosive esophagitis, esophageal ulcer, or peptic stricture, should generally not be considered for PPI discontinuation.
Best Practice Advice 5 Patients with known Barrett’s esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis should generally not be considered for a trial of de-prescribing.
Best Practice Advice 7 Patients at high risk for upper gastrointestinal bleeding should not be considered for PPI de-prescribing.
Best Practice Advice 10 The decision to discontinue PPIs should be based solely on the lack of an indication for PPI use, and not because of concern for PAAEs (PPI-associated adverse events).
My take: There are a lot of individuals who could benefit from de-prescribing PPIs.
Researcher’s have utilized viruses to introduce exogenous DNA in efforts to correct defects in genetic diseases. Adeno-associated virus (AAV) vectors are the most common vectors used. In addition, AAV have a natural tropism to the liver following intravenous infusion
“Highlighting programs with the most advanced efficacy, hemophilia gene therapies in the liver have advanced into phase 2/3 and have shown promising efficacy based on factor VIII or IX levels achieved and reduction in bleeding events, with the main questions being long-term expression and safety of the approach”
Limitations:
“Integrated AAV have been associated with an increased incidence of hepatocellular carcinoma in mice”
Antibodies to AAV may be present or develop after infusion…” this factor has precluded any redosing in trials because antibodies would neutralize all incoming vectors”
In hemophilia trials, in the liver there has been a slow decrease in the levels of expression over time 6 which indicates that years into the future patients will need to be redosed to maintain efficacy
“Practically, AAV can only achieve delivery in a fraction of cells within an organ”
Newer Approaches for Gene Delivery:
mRNA delivery: mRNA is being explored as a tool for gene therapy, because mRNA only requires cytoplasmic delivery for expression.
“mRNA can also express gene-editing enzymes like Cas9….However, gene editing presents inherent risks of off-targeting cutting or base editing that would occur in millions of hepatocytes, potentially leading to cancer”
“Nonviral approaches of DNA delivery could drop the costs of vector production at least 100-fold versus AAV…delivery of DNA through LNPs [lipid nanoparticles] has largely yielded inefficient gene expression”
“Hydrodynamic injection is a process where fluid pressure is used to deliver naked DNA directly into cell…injection into the biliary system through endoscopic retrograde cholangiopancreatography”
The authors note that gene delivery could be important in modifying more common disorders including nonalcoholic steatohepatitis, diabetes and autoimmune diseases.
My take: While this field of study is quite exciting, to me it is definitely a shiny object, like all of precision medicine, in that it may distract researchers and physicians away from more pressing common problems.
“Issue-attention cycle” problem. “This pattern occurs when initial public alarm over the discovery of a problem and optimism about its quick resolution are replaced by the realization that solving the problem will require some public sacrifice and will displace powerful societal interests.”from Weight of the Nation | gutsandgrowth
This commentary notes that the National Institutes of Health (NIH) spends more than $40 billion each year to fund biomedical research. “We believe that medicines discovered at public expense should be affordable.”
A Few Excerpts:
“Existing laws provide two paths for achieving this result. First, the Bayh–Dole Act of 1980 gives the government a royalty-free license to use patented inventions that were discovered using federal funding. The government has never exercised its Bayh–Dole license”
“Second, 28 U.S. Code §1498, which dates to 1910, gives the government immunity from being sued for patent infringement in federal courts, while giving patent owners the right to receive reasonable compensation when the government makes or uses a patent-protected product”
Case in point: “Recently, the government signed a contract with Merck to purchase molnupiravir (Lagevrio), an oral antiviral drug that reduces the severity of Covid-19. The contract price of $712 per treatment is estimated to be more than 35 times the cost of producing the drug at a reasonable profit. Molnupiravir was discovered at Emory University using government funding, and Emory’s patent applications acknowledge the government’s Bayh–Dole license.5 Molnupiravir payments for Medicare, Medicaid, and VHA patients could cost the government billions in 2022. This amount could be reduced by more than 90% if the government exercised its license and allowed a generic manufacturer to supply the drug for patients in government-supported programs.”
My take: U.S. taxpayers should get a return on their investment when new medications are developed with government funding rather than paying more for these medications than any other country.
