Reassuring Study of Infants Exposed to Biologics

Posted on July 5, 2026 by gutsandgrowth

L Palomino et al. Clin Gastroenterol Hepatol 2026; 24: 1688-1701. Open Access! Psychomotor Development in Infants Following Maternal Exposure to Biologics: Results From the DUMBO Registry

Methods: DUMBO (NCT03894228) is an ongoing, prospective, multicenter, observational registry study supported by Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) which includes women with IBD whose pregnancy was known to the investigator before the 28th week of gestation. Psychomotor development of infants was assessed using the Spanish version of the Ages and Stages Questionnaire 3rd edition (ASQ-3) during the first year of life.

Key findings:

Exposure to biologics in utero, had no impact on ASQ-3 scores at month 12.
Multivariate analysis revealed that preterm birth (odds ratio, 0.3; 95% confidence interval, 0.1–0.6) and maternal ulcerative colitis (odds ratio, 0.5; 95% confidence interval, 0.3–0.9) were associated with an increased risk of abnormal ASQ-3.

Discussion Points:

“Active maternal inflammation during the periconception period and pregnancy has been associated with low birth weight, preterm delivery, small size for gestational age, spontaneous abortion, and stillbirths.³^,⁴…Active maternal inflammation during the periconception period and pregnancy has been associated with low birth weight, preterm delivery, small size for gestational age, spontaneous abortion, and stillbirths.³^,⁴“
“In infants born to mothers with IBD, exposure to biologics would be expected to reduce their exposure to inflammatory cytokines in utero, which could potentially mitigate the impact of maternal inflammation on psychomotor development… our study found no negative impact of biologics exposure on the psychomotor development of infants, either from exposure in utero or during breastfeeding. Furthermore, we observed higher ASQ-3 scores in the personal-social domain at 4 months and in the gross and fine motor domains at 12 months in biologics-exposed vs nonexposed children, possibly reflecting a beneficial effect of treatment in reducing maternal inflammation.”
“Data from the PIANO study further supports our findings. Mahadevan et al assessed psychomotor development in 206 children exposed to biologics (both anti-TNF and non-anti-TNF) in utero, and 92 controls, finding higher ASQ-3 scores in the exposed group.”

My take: Biologic exposure does not appear to impair psychomotor development in infants. While this study provides useful information, I am not impressed wtih with the Acronym DUMBO for this registry.

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“Real-World” Impact of Vitamin D for Patients with Inflammatory Bowel Disease

Posted on July 3, 2026 by gutsandgrowth

JA Sninsky et al. Clin Gastroenterol Hepatol 2026; 24: 1666-1674. Open Access! The Real-World Impact of Vitamin D Supplementation on Inflammatory Bowel Disease Clinical Outcomes

Methods: This was a retrospective cohort study of adult patients (n=5021) with IBD seen in the national Veterans Health Administration system from 2000 to 2023. The researchers used 3 different methods to try to determine causality of improved outcomes with supplementation of Vitamin D.

“Difference-in-differences (DiD) approach to compare changes in clinical outcomes before and after vitamin D testing between patients who did and did not receive supplementation”
“The regression discontinuity design leveraged the clinical threshold of 30 ng/mL serum 25-hydroxyvitamin D, comparing outcomes in patients just lower than and just higher than this cutoff, who are assumed to be otherwise similar”
“The inverse probability weighting method adjusted for confounding by weighting patients based on their likelihood (propensity) of receiving vitamin D¹⁵“

Key findings:

The median 25-hydroxyvitamin D level was 23 ng/mL, and 41% received vitamin D supplementation
Vitamin D supplementation was associated with reduction in IBD-related emergency department visits by 2.17% (34.4% relative risk reduction; P = .007), hospitalizations by 2.64% (53.18% relative risk reduction; P = .003), and corticosteroid prescriptions by 1.29% (25.13% relative risk reduction; P = .066)

Discussion:

“Collectively, our data strongly suggest that vitamin D supplementation reduces the risk of IBD flare, underscoring its promise as an effective adjunctive therapy in clinical practice.”
“Vitamin D deficiency is prevalent among patients with IBD and is strongly linked to poor clinical outcomes, including higher rates of hospitalization and surgery. Patients with IBD are 64% more likely to be vitamin D deficient compared with healthy control subjects.²⁹“
“Vitamin D deficiency is prevalent among patients with IBD and is strongly linked to poor clinical outcomes, including higher rates of hospitalization and surgery. Patients with IBD are 64% more likely to be vitamin D deficient compared with healthy control subjects.²⁹“
“Although these findings support a strong association between vitamin D deficiency and worse clinical outcomes, they do not address whether supplementation itself mitigates the risk of adverse events, because disease severity confounds this relationship.³³ Our study fills this knowledge gap and provides rigorous real-world data to support the effectiveness of vitamin D supplementation.”

My take: There have been large studies (eg. VITAL) study showing that Vitamin D supplementation does not help most people in the general population. In addition, many individuals with IBD who have low Vitamin D levels may see improvement in Vitamin D status by treating the IBD (without Vitamin D supplement). Yet, studies like this one by Sninsky indicate that Vitamin D supplementation is associated with improved outcomes in this retrospective cohort; the study methods likely indicate a causal effect of supplementation; however, a prospective randomized controlled study would be more definitive.

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Here’s Why CYP2C19 Testing May Be Helpful For Refractory Reflux

Posted on July 2, 2026 by gutsandgrowth

Recent pediatric Rome V recommendations suggested the use of CYP2C19 testing in patients with reflux that was not responding to time-limited therapy (link: Rome V Pediatric Upper Gastrointestinal Disorders of Gut-Brain Interaction (Part 1)). The following retrospective study of adults (n=421) at an academic medical center provides a strong rationale.

L Creech et al. Clin Gastroenterol Hepatol 2026; 24: 1550-1557. Open Access! High Prevalence of CYP2C19 Rapid and Ultrarapid Metabolism Among Patients With Gastroesophageal Reflux Disease

Key finding:

44% (n=184) of patients presenting to gastroenterology clinic with gastroesophageal reflux disease who underwent CYP2C19 genotyping were found to be rapid metabolizers (RMs) (38%) or ultrarapid metabolizers (6%)
The prevalence of Barrett’s esophagus/erosive esophagitis was higher among ultrarapid metabolizers (24%; n = 5/21) than among normal metabolizers (7%; n = 12/165; odds ratio, 3.5)
Among the 184 RMs, 79% (n = 146) had a change in management due to CYP testing results: 65% (n = 120) changed their medication (89 patients were switched to rabeprazole), 22% (n = 41) continued PPI therapy, and 14% (n = 26) increased their PPI dose

Discussion points:

Prevalence of CYP RMs in Other Studies:

“Ionovo et al studied over 2 million patients who underwent genetic testing using 23andMe and found that the rate of RMs (∗1/∗17) in the general population was 26.0%, and the rate of URMs (∗17/∗17) was 4.4%.²⁵“
“Fricke-Galindo et al analyzed data from 138 studies of over 52,000 healthy volunteers from around the world.²⁶ The highest rates of combined RMs and URMs were reported in the Middle Eastern populations (36%), followed by European (28.6%), African (16.8%), and Asian populations (3.4%).²⁶ The prevalence was 26.7% in the United States.”

“Among GI clinical practice guidelines, the 2025 American Society for Gastrointestinal Endoscopy (ASGE) guideline was the first to suggest routine incorporation of CYP testing into the management of patients with GERD.³⁰“
“PCABs offer a viable alternative to PPIs in patients who are RMs and should be considered accordingly. PCABs are also not dependent on preprandial dosing and thus are easier for patients to take. However, the cost of PCABs continues to be a limiting factor.”
Testing cost: “A typical out-of-pocket price of $250 to $400 and is covered by some insurance.³⁹“
Limitations: The study population has a selection bias compared to the general population. Patients referred to a GI clinic are more likely to have treatment-refractory GERD and thus have higher rates of RMs.

My take: In patients with established GERD who are not responding to treatment, CYP testing may be helpful. This is probably true for patients with EoE as well. In patients with GERD who are RMs, options include changing to rabeprazole, higher doses, or possible use of PCABs.

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Pediatric Experience with Subcutaneous Infliximab

Posted on July 1, 2026 by gutsandgrowth

EH Boute et al. Inflamm Bowel Dis 2026; 32: 1086–1096. Open Access! Persistence and safety of subcutaneous infliximab up to 1 year after switching from intravenous infliximab in pediatric inflammatory bowel disease: a multicenter real-world cohort study

Methods: This was a retrospective multicenter study we identified pediatric IBD patients (n=66 including 41 with Crohn’s disease) who switched to SC-IFX. Median age 16.5 years. Pre-switch, the median IV-IFX maintenance dose was 10 mg/kg every 6 weeks. There were only 6 patients with a weight <40 kg.

Key findings:

The initial SC-IFX regimen was 120 mg every other week in 62/66 patients (94%). 4 patients (6%) were initiated on 120 mg every week
SC-IFX persistence was 78% at 12 months post-switch, with 89% of patients persisting on IFX, either intravenous (IV) or subcutaneous (SC), at the end of follow-up
17% (n=11) of patients experienced relapses. 6 patients underwent dose intensification (3 regained response), 3 patients switched to a different advanced therapy, and 3 patients received concomitant therapy
11 patients (17%) discontinued SC-IFX treatment after a median of 7.0 months
6 patients underwent SC-IFX dose intensification, with 3 successfully regaining clinical response
Regarding anti-drug antibodies (ADA), 3 out of 4 patients who were ADA positive on IV-IFX resolved post-switch
Three patients (3/66, 5%) experienced serious AEs requiring hospitalization, namely IgA-mediated nephropathy, pyelonephritis requiring IV antibiotics, and perianal fistula requiring seton drainage

Discussion:

“Compared to IV-IFX, SC-IFX provides higher and more stable serum concentrations, avoiding peak-trough variability, potentially lowering immunogenicity and offering greater flexibility in TDM.”
“Careful monitoring by the IBD team remains essential to ensure treatment adherence during and after the switch. In our cohort, most discontinuations (64%) were related to difficulties with the SC route, highlighting the importance of identifying the most suitable candidates.”

My take: More pediatric studies are needed. This study suggests that the effectiveness of SC-IFX in children will be similar to the effectiveness in adults. As more patients receive SC therapy, it will be particularly important to work on adherence with scheduled dosing, lab monitoring, and careful followup visits; all of these can be more difficult with SC compared with IV infusions.

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Data Insufficient to Recommend Immobilized Lipase Cartridge Use in Children with Short Bowel Syndrome

Posted on June 30, 2026 by gutsandgrowth

E Khenner et al. J Pediatr Gastroenterol Nutr. 2026;82:1488–1494. Open Access! Retrospective chart review of immobilized lipase cartridge use in children with short bowel syndrome

***Three of the authors of this study are/were employed or receive research support from Alcresta Therapeutics, Inc.

This small retrospective single-center study reports the use of in-line immobilized lipase cartridges (ILC) in 14 patients; 10 were PN-dependent, and four had enteral autonomy (Table 1). The mean age at the start of ILC use was 6 years (range 2–15 years). Mean estimated residual small bowel length was 66 cm (range 11–190 cm; n = 13). Eight patients received peptide-based EN and 6 elemental EN, typically delivered over 12–24 h.

Key findings:

In 9 PN-dependent patients (with Type II or III SBS), mean PN use at baseline was 45.3 kcal/kg/day (59% of supplemental nutrition). At final follow-up, mean PN use decreased by 10.6 kcal/kg/day (15.5%) and mean EN use increased by 6.0 kcal/kg/day (39.9%) after 3.8 to 23.9 months of ILC use.
In 4 patients with enteral autonomy (all Type III SBS), mean weight z-score improved by 0.60 and mean EN use decreased by 6.9% after 2.7 to 5.3 months of ILC use. The decrease from baseline in mean EN use at final follow-up was driven by data from one patient (#12) who had poor compliance with tube feeding.
None of these changes are statistically significant.

Discussion:

“There are limitations to ILC use in children with SBS: not all SBS patients receive EN, bolus feeding with ILC is limited to flow rates ≤400 mL/h, and ILC is not compatible with high fiber enteral formulas.⁶“
“Blenderized tube feeding is becoming the preferred method of enteral feeding in pediatrics.¹⁷ Although the use of blenderized tube feeds in children with SBS is associated with improved GI symptoms as well as a reduction in PN dependence, some patients experience intolerance or lack of weight gain.^18, 19“
The authors conclusions: “ILC offers a low-risk option to potentially advance enteral autonomy or weight gain in some children with SBS.”

My take: I am not convinced that ILC is worthwhile for pediatric patients with SBS. I have received questions about this from our neonatal colleagues. When I have questioned leaders of several intestinal rehab centers, they have stated there is no solid data supporting its use. When I have asked the manufacturer to provide data in children with SBS less than two years of age, I have heard no response. The cost (without insurance) likely exceeds $9,000/month if using two ILCs per day. The use of this expensive product needs to be carefully evaluated in a prospective randomized trial.

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BAPS Shri Swaminarayan Mandir, Atlanta (Hindu Temple)

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. 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

Oral Vancomycin For Pediatric Inflammatory Bowel Disease

Posted on June 29, 2026 by gutsandgrowth

S Ancona et al. J Pediatr Gastroenterol Nutr. 2026;82:1416–1426. Effectiveness and safety of oral vancomycin in non-primary sclerosing cholangitis paediatric inflammatory bowel disease

Background: “Oral vancomycin (OV) has limited usage in paediatric inflammatory bowel disease (PIBD) with reported efficacy in primary sclerosing cholangitis (PSC-PIBD), acute severe colitis as part of quadruple-antibiotic regimen, and very early-onset IBD. This study evaluates OV effectiveness and safety as a single-agent in non-PSC PIBD.”

Methods: Retrospective, single center study with 31 children (median age 15.1); the presence of PSC and C diff were exclusion criteria. There were 23 ulcerative colitis (UC), 4 IBD-unclassified (IBDU) and 4 Crohn’s disease. OV was started at 250 mg for patients ≥30 kg or 125 mg for those <30 kg and administered four times daily (QDS) or three times daily (TDS). The majority were receiving concomitant medications: steroids in 16%, biologics in 32%, 5-ASA in 74%, and thiopurines in 42%.

Key findings:

Clinical and biochemical remission was achieved or maintained in 17/31 (55%), with 15/17 reducing/stopping other treatments and two remaining on OV monotherapy
At 1-month faecal calprotectin dropped from 686 to 60 μg/g in responders (p = 0.001) but remained high in nonresponders
Responders (Group 1) continued OV for a median of 7.0 months (IQR 2.5–23.5), maintaining consistently low PUCAI and FC levels throughout a median follow‐up of 19.0 months. After discontinuation, three relapsed and restarted OV,recapturing remission in 2/3.
Responders had lower baseline clinical disease activity
No serious adverse events occurred. No vancomycin-resistant enterococcus (VRE) colonization was seen

My take: This study’s vancomycin responders (55%) had significant improvement within four weeks. This is in agreement with other studies indicating that antimicrobial regimens may be helpful in a significant subset of children with inflammatory bowel disease. Larger prospective studies are warranted.

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Linaclotide Now FDA-Approved for 2-5 Year Olds with Functional Constipation

Posted on June 28, 2026 by gutsandgrowth

Ironwood Pharmaceutical Press Releasse, 5/27/26: FDA Approves Use of LINZESS® (linaclotide) in Pediatric Patients Two Years of Age and Older with Functional Constipation (FC)

An excerpt:

Expanded indication extends availability to children ages 2-5 with FC; previously approved in pediatric patients 6 years of age and older –
– LINZESS remains the first-and-only FDA-approved prescription therapy for pediatric FC…

Parents can mix the contents of the LINZESS capsule with applesauce or water, providing flexibility for administration in young children...

The FDA approval for pediatric patients ages 2-5 was supported by data from a 12-week Phase 3 randomized, placebo-controlled clinical trial evaluating LINZESS in pediatric patients aged 2-5 years with FC. In the study, LINZESS 72 mcg demonstrated improvement in spontaneous bowel movement frequency compared with placebo. The safety profile of LINZESS observed in the trial was generally consistent with the established safety profile from trials in adults with chronic idiopathic constipation (CIC) and older pediatric patients with FC...

LINZESS 72mcg is available as a once-daily treatment of FC for pediatric patients 2 years of age and older

My take: In this age group, typical over-the-counter laxatives including polyethylene gylcol, magnesium products, and senna products along with diet and behavior modification will be effective for most children. Most children will not need a prescription medication to manage their constipation.

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Association Between Hypermobility Disorders, Orthostatic Intolerance and DGBIs

Posted on June 26, 2026 by gutsandgrowth

N Santucci et al. J Pediatr Gastroenterol Nutr. 2026;82:1394–1399. Open Access! Children and adolescents with disorders of gut–braininteraction with comorbid hypermobility and orthostaticintolerance have worse outcom

Methods: This was a retrospecitive study from a multidisciplinary pediatric DGBI clinic which examined the relationship between hypermobility spectrum disorders (HSDs) and orthostatic intolerance (OI). HSD terms included Ehlers–Danlos syndrome, hypermobile Ehlers–Danlos syndrome, and generalized hypermobility; OI terms included postural orthostatic tachycardia syndrome, dysautonomia, and orthostatic hypotension. Of 175 patients, 46% had HSD and 43% had OI; 26% had both HSD and OI.

Key findings:

Patients with both HSD and OI had significantly worse nausea, depression, disability, and somatization scores than others (p < 0.01).
HSD and OI groups individually also showed worse outcomes than non-HSD/non-OI groups. Moderate correlations were found between depression and anxiety in OI and nausea and disability in HSD.
Patients with both HSD and OI (n=45) had worse NSS (p < 0.0001), PHQ-9 (p = 0.007), FDI (p = 0.001), and CSI (p < 0.001) compared to patients with either OI or HSD and patients with neither.

Discussion:

“Autonomic dysfunction may explain the shared GI symptoms for OI and HSD patients. GI blood flow, motility, and secretion are regulated by an integral neural mechanism involving inputs from the central nervous system and the enteric nervous system. “
“Formal diagnosis of HSD and OI can be challenging and often requires involvement of multiple subspecialists…Studies comparing these groups run the risk of under-reporting diagnoses or including patients without the diagnosis. Strict clinical criteria are required using guidelines.”
There may be a selection bias for these patients in a specialized clinic for DGBIs; this was not discussed in this article. There is likely an increased rate of screening for HD and OI in patients with more severe DGBIs given previous reports of association with DGBIs.

My take: HSDs and OI are highly prevalent in DGBIs. In this study, both of these disorders were associated with worsened symptoms.

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Marked Variation with Vibration Controlled Transient Elastography in Pediatric Metabolic Dysfunction Associated Steatotic Liver Disease

Posted on June 25, 2026 by gutsandgrowth

Background: “Given the invasiveness of liver biopsy, the development of accurate non-invasive biomarkers of MASLD severity remains an area of active investigation… clinical practice has been shifting towards the use of point-of-care vibration controlled transient elastography (VCTE), based on extensive cross-sectional and longitudinal validation data in adults.¹¹ However, despite increasing clinical use of VCTE to determine MASLD presence and severity in children, this technique lacks well-validated cut-points in this age range and, importantly, there are no data evaluating the implications of longitudinal changes.^12–15…While a high (>12 kPa) LSM is concerning for progression to advanced fibrosis in adults,¹¹ the optimal cutoff for defining an elevated LSM in pediatric MASLD has yet to be established.^16, 17“

Methods: This was a longitudinal retrospective study of youth (n=149, mean age 14 yrs) with MASLD who underwent ≥2 VCTE studies.

Key findings:

Controlled attenuation parameter (CAP) and liver stiffness measurements (LSMs) showed marked intraindividual variability.
Changes in CAP and LSM did not predict categorical outcomes of ALT and GGT reduction, however were significantly positively associated with continuous ALT and GGT outcomes, independent of BMI percentile.

Individual variation in mean controlled attenuation parameter (CAP; panel A) and liver stiffness measures (LSM; panel B) over time. Solid black lines represent Loess lines.

My take (borrowed in part from the authors): “Given the substantial intra-individual variation and the current lack of validated definitions for clinically significant change in VCTE measures (CAP and LSM) in children with MASLD, serial VCTE measurements in individual pediatric patients should be interpreted with caution and not relied upon in isolation for clinical decision-making.”

While transient elastography is not reliable in pediatric MASLD, a related article suggests that it is helpful for pediatric autoimmune hepatitis: W Janczyk et al. J Pediatr Gastroenterol Nutr. 2026;82:1349–1356. Transient elastography for accurate staging of liverﬁbrosis and predicting complications in children withautoimmune hepatitis

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Cyproheptadine: “Vitamin P”

Posted on June 24, 2026 by gutsandgrowth

C Baker et al. J Pediatr Gastroenterol Nutr. 2026;82:1321–1324. Cyproheptadine: The secret sauce

Mechanism of action:

A first-generation antihistamine with anti-cholinergic, anti-serotonergic, and local anesthesia properties; its precise mechanism of action is poorly understood.

Formulation/pharmocokinetics:

Enteral tablet and syrup formulations appear to be well absorbed with peak serum levels 6–9 h after dosing in adults.² However, anecdotally in pediatrics, the side effect of somnolence is often felt much more quickly.

Uses (off-label):

Promote weight gain: “There is ample literature to support success in varying populations, including mild to moderately undernourished toddler-aged children and children with cystic fibrosis.^4–6“
Cyclic vomiting syndrome
Functional abdominal pain and dyspeptic symptoms
Post-operative Retching After Fundoplication

Dosing (by indication):

“For cyclic vomiting syndrome prophylaxis, the recommended dose is 0.25–0.5 mg/kg/day divided every 8–24 h with a maximum dose of 12 mg a day.”
“For appetite stimulation, the recommended dose is 0.25 mg/kg/day divided twice daily, with a maximum dose ranging from 12 to 32 mg depending on patient age.”
“An effective dosing range for use in disorders of the gut–brain interaction (DGBIs) in pediatric patients (median age 9 years) of 0.13–0.2 mg/kg/day has been reported when used on average for 9 months, with a mean initial dose of 4.85 mg/day and final dose of 5.34 mg/day.¹“
“A large, systematic review from France identified the median dose for all pediatric clinical indications to be 0.25 mg/kg/day…Many clinicians use once-daily dosing to improve adherence.”

Contraindications, Drug Interactions, and Complications:

“Cyproheptadine is contraindicated in newborns and premature infants due to the potential for CNS depression and a lack of evidence in its safety and efficacy.”
“Cyproheptadine has potential for multiple drug-drug interactions, and dose adjustments may be required with concomitant therapies.”
“Recent publications suggest that up to 30% of patients will experience mild and self-limited side effects while taking cyproheptadine.⁸ The most common side effects are somnolence, increased appetite, weight gain, and behavior changes.^1, 8 Caution should be exercised in the use of cyproheptadine in children who are already considerably overweight…A rare side effect of adrenal insufficiency…has been documented in pediatric patients.”

My take: Because cyproheptadine is so useful for pediatric GI disorders, some of my colleagues have referred to it as “Vitamin P” (periactin). This review provides a lot of helpful data and guidance.

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. 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