Tag Archives: Ulcerative colitis

Pediatric Guidelines for Ulcerative Colitis (Part 1)

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E Wine et al. JPGN 2025;81:765–815. Open Access! Management of paediatric ulcerative colitis, part 1: Ambulatory care—An updated evidence-based consensus guideline from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn’s and Colitis Organisation

This is the first of two highly-detailed papers. (This is a 50 page report.) it has extensive/comprehensive recommendations and information on all aspects of UC management, except acute severe colitis which is covered tomorrow.

Here are some of the recommendations:

  • Thiopurines are recommended for maintaining remission in children who, despite optimal 5-ASA treatment, are corticosteroid-dependent or have frequent relapses (≥2 relapses per year) or in 5-ASA-intolerant patients; thiopurines should be considered following discharge from ASC episodes (EL4, adults EL3) (Agreement 100%).
  • Infliximab should be considered, preferably in combination with an IMM, as the first-line biologic agent in chronically active or corticosteroid-dependent UC, uncontrolled by 5-ASA, and in most cases also thiopurines, for both induction and maintenance of remission [EL1, adults EL1] (Agreement 96%).

It is worth noting that anti-TNF monotherapy with pTDM is common practice in the U.S. due to concerns about the safety of combined therapy with a thiopurine (Related blog post: Can Therapeutic Drug Monitoring with Monotherapy Achieve Similar Results to Combination IBD Therapy?). These pediatric guidelines with regard to combination therapy are similar to recent ACG guidelines for adults (D Rubin et al. The American Journal of Gastroenterology 120(6):p 1187-1224, June 2025. Open Access! ACG Clinical Guideline Update: Ulcerative Colitis in Adults).

  • Infliximab is recommended to be used preferably in combination with an IMM (with the most evidence in UC being for thiopurines) to reduce the likelihood of developing antibodies to infliximab (ATIs) and in thiopurine-naïve patients, to enhance effectiveness. Methotrexate may also be used to mitigate ATIs. For immunogenicity prevention, lower doses of azathioprine (1–1.5 mg/kg) may be used. Data on methotrexate dose in this setting are scarce, but low total doses of 7.5–12.5 mg weekly are reported. Proactive TDM is recommended, particularly when infliximab is prescribed as monotherapy (Agreement 96%).
  • In most cases, higher doses of infliximab (e.g., 10 mg/kg/dose at Weeks 0, 2 and 6, followed by 10 mg/kg every 4–8 weeks for maintenance) are required to provide the best chance of reaching the desired clinical and endoscopic outcome. The dose can be subsequently reduced, guided by TDM. Lower dosing (5 mg/kg) can be used in less severe cases. In cases in which IV infliximab treatment is switched to subcutaneous injections, the recommended dosing schedule (established only for >40 kg) is 120 mg every 2 weeks. See Table 2 for dosing details (Agreement 100%).
  • Proactive TDM is recommended for both infliximab and adalimumab, particularly at the end of induction (before the 4th infliximab infusion and after 3 adalimumab injections) [EL4] (Agreement 100%).

Cancer Surveillance:

  • 1. Children with UC aged 12 years and over with a disease duration of greater than 8 years should be considered for surveillance for CRC and dysplasia [EL4, Adults EL1] (Agreement 96%).
  • 2. Children with UC and PSC should be considered for surveillance for CRC and dysplasia starting at age 12, regardless of disease duration [EL4, Adults EL3] (Agreement 100%).

My take: The referenced paper in today’s post and tomorrow’s are essentially updated published book chapters with specific management recommendations. There are likely some practice variations but overall the recommendations will help garner support for current practices like optimizing infliximab dosing and using proactive TDM.

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

What Caught My Eye in a Recent Anti-IL23 Commentary

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This recent commentary on the all-subcutaneous induction and maintenance treatment with guselkumab, an anti-IL23 agent, reviewed the GRAVITI study. Related post: Guselkumab for Crohn’s Disease: Pivotal GRAVITI Study

However, what captured my attention was the last sentence: “The convenience of subcutaneous induction enhances patient friendliness, positioning guselkumab as a strong market contender. Could an oral anti–IL-23 formulation be the next game changer?14“

“Johnson & Johnson (NYSE: JNJ) today announced positive topline results from ANTHEM-UC, a Phase 2b study of icotrokinra (JNJ-2113), the first investigational targeted oral peptide that selectively blocks the IL-23 receptor, in adults with moderately to severely active ulcerative colitis (UC)…

In the ANTHEM-UC study (n=252), three doses of once daily icotrokinra were tested with all meeting the primary endpoint of clinical response at Week 12. A response rate of 63.5% for patients treated with the highest dose of icotrokinra was achieved at Week 12 versus 27% for placebo (p<0.001). Further, 30.2% of patients treated with the highest dose of icotrokinra demonstrated clinical remission at Week 12 versus 11.1% of patients who received placebo (p<0.01). Remission and response rates continued to improve through Week 28.

  • Clinical response is defined as decrease from baseline in the modified Mayo score by greater than or equal to (>=) 30 percent (%) and >=2 points, with either a >=1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.
  • Clinical remission is defined as a Mayo stool frequency subscore of 0 or 1 and not increased from induction baseline, a Mayo rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1 with no friability present on the endoscopy.”

My take: It would be terrific for patients with inflammatory bowel disease (and other immune-mediated diseases) to have another excellent oral therapy. A prior study of plaque psoriasis indicated that an oral IL-23 medication is feasible (Related post: In Trials: An Oral IL-23 Antagonist Peptide).

Related joke (regarding “caught my eye” in the title of this post):

A man who lived in a block of apartments thought it was raining and put his head out the window to check.  As he did so a glass eye fell into his hand. He looked up to see where it came from in time to see a young woman looking down. “Is this yours?” he asked.

She said, “Yes, could you bring it up?” and the man agreed. On arrival she was profuse in her thanks and offered the man a drink. Shortly afterwards she said, “I’m about to have dinner.  There’s plenty; would you like to join me?” He readily accepted her offer and both enjoyed a lovely meal. As the evening was drawing to a close the lady said, “I’ve had a marvelous evening.  Would you like to stay the night?”  The man hesitated then said, “Do you act like this with every man you meet?”

“No,” she replied, “only those who catch my eye.”

The Manneporte by Claude Monet (at the Metropolitan Museum of Art)

Sulfasalazine vs 5-ASA: Treatment Outcomes in Pediatric UC

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I Mansuri et al. J Pediatr Gastroenterol Nutr. 2025;80:988–997. Clinical outcomes of maintenance therapy with sulfasalazine compared to 5-aminosalicylates in children with ulcerative colitis

Methods: This was a retrospective review of children diagnosed with UC between June 1999 and December 2019 at Boston Children’s Hospital. 124 started on sulfasalazine (SZ) and 309 on 5-aminosalicylates (5-ASA). Most patients had mild to moderate disease based on PUCAI score; ~12% had severe disease.

Key findings:

  • At 1 year, 54%, 44.3%, and 36.6% of patients on SZ, 5-ASA, and those who switched, respectively, were in steroid-free remission (p = 0.13)
  • All medication switches due to adverse reactions (24) were from SZ to 5-ASA. No patient was switched from 5-ASA to SZ because of adverse reactions. The non-severe adverse reactions noted were nausea, vomiting, abdominal pain, non-severe skin rash, headache, mild leucopenia, and lymphadenitis. Three patients had serious skin reactions, and one had pancreatitis.
  • SZ tended to have more minor adverse reactions. Except for countering adverse reactions, switching between SZ and 5-ASA did not offer therapeutic benefits. Disease severity at diagnosis predicted early treatment escalation

Discussion Points:

  • SZ offers advantages such as lower cost and availability in suspension form; the suspension form is particularly beneficial for young children and those unable to swallow the solid form of medication.
  • 5-ASA formulations can be almost 10–50 times more expensive than SZ. For example, the wholesale acquisition cost of monthly generic SZ is $30 compared to $274 for generic Lialda, $1131 for generic Pentasa, and $1890 for generic Asacol HD

My take: About 20% of patients had to switch from Sz to 5-ASA due to adverse reactions; though, Sz had a mildly higher response rate (not statistically-significant). Switching between SZ and 5-ASA or vice versa is unlikely to provide much therapeutic benefit; patients who switched agents for medical reasons (rather than reactions) were more likely to require escalation to either a biologic or immune modulator.

Related blog posts:

Chatttahoochee River (Sandy Springs)

Understanding the Prevalence and Burden of Pediatric Inflammatory Bowel Disease in U.S.

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 From editorial (which is more expansive than the study):

Kappelman et al4 report the US prevalence of pediatric-onset IBD (diagnosed before the age of 20 years by a physician) as well as rates of disease based on race and ethnic background. To ensure that a representative population was captured, they combined multiple health administrative databases…

The authors report that the US currently has a pediatric IBD prevalence of 125 per 100,000 population, increased from 110 per 100,000 in 2011. This is higher than previously reported in Canada (82 per 100,000 in 2023)6 and Sweden (75 per 100,000 in 2010).7 These differences may be due to the older age cutoff used in the US data, <20 years vs <18 years in the Canadian and Swedish studies. However, misclassification bias may also play a role...

Nevertheless, understanding the approximate prevalence of pediatric IBD in the US allows for adequate human and financial resource planning for this important population of children with an impactful chronic disease. The high prevalence should raise concerns among health care practitioners and policy makers that we have under-resourced IBD care in children, especially considering the high rate of use of biologics and the growing direct health costs incurred in the treatment of this population.11

The burden of IBD in pediatrics goes beyond that of the child. Compared with adult IBD, it disproportionately affects caregivers and families (owing to missed work for appointments, hospitalizations, and home care), mental health of both the patient and the parents, and the health system...

They report that pediatric IBD is more frequent among White children and adolescents (145 per 100,000) compared with Black (91 per 100,000) and Hispanic (88 per 100,000) children, whereas children of Asian origin have markedly lower rates (52 per 100,000).“

My take: The updated prevalence data helps understand the increasing frequency of pediatric IBD. The associated commentary reminds us of the broader burden the disease has for families and for our communities.

Related blog posts:

Constipation Preceding a New Diagnosis of Inflammatory Bowel Disease

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S Cenni et al. J Pediatr Gastroenterol Nutr. 2025;80:799–806. The prevalence of constipation in children with new diagnosis of inflammatory bowel disease: A retrospective study

This was a cross-sectional observational study in pediatric IBD-patients (n=238) with 104 (43.6%) with Crohn disease (CD), 130 (54.6%) with ulcerative colitis (UC) and 4 (1.6%). Only patients who filled out the Rome IV questionnaire for FC, through dedicated symptom recall at the next clinic appointment or telephone recall, were finally enrolled in the study for subsequent analysis.

Key findings:

  • Forty-seven out of 238 (19.7%) had a functional constipation history before the IBD diagnosis. In the CD children the prevalence of constipation before the IBD diagnosis was 19/104 (18.2%) and in the UC patients was 28/130 (21.5%).
  • The difference in terms of endoscopic localization was statistically significant in UC patients presenting FC (p = 0.026) with a prevalence of proctitis and left side colitis (30% and 15%, respectively)
  • There was a delay in the diagnosis of patients with preceding constipation

Discussion Points:

  • The main limitations of the present study are certainly related to the retrospective nature and, therefore, the possibility of recall biases must be taken into account.
  • Rectal bleeding that persists despite stool softener therapy should be investigated

My take: While this study shows that constipation is fairly common prior to a diagnosis of IBD, many times a parent is told that their child is constipated on the basis of an xray or simply because the child complained of stomach pain. This likely increases the risk of recall bias. My guess is that a prospective study involving careful questioning at the time of the initial colonoscopy would yield a lower number of children who had constipation at the time of diagnosis.

Related blog posts:

Set of Shucked! at The Fox Theater. Really enjoyed this ‘corny’ musical.

Long-term Efficacy and Safety of Upadacitinib for Ulcerative Colitis

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R Panaccione et al. The Lancet Gastroenterology & Hepatology. 2025; 10: 507 – 519. Open Access! Long-term efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis: an interim analysis of the phase 3 U-ACTIVATE long-term extension study

Methods: U-ACTIVATE is an ongoing, 288-week, phase 3, long-term extension study that enrolled patients (n=369) aged 16–75 years with a confirmed diagnosis of moderately to severely active ulcerative colitis; patients who had a clinical response in the induction studies were eligible to enter the U-ACHIEVE maintenance study. Patients not in clinical remission originally randomly assigned to upadacitinib 15 mg were eligible to escalate to upadacitinib 30 mg, those originally randomly assigned to upadacitinib 30 mg continued on upadacitinib 30 mg, and those originally assigned to placebo were eligible to escalate to upadacitinib 15 mg in a masked way

Key findings:

  • In the as-observed population, 84 (71%) of 118 patients receiving upadacitinib 15 mg were in clinical remission at week 48, as were 130 (67%) of 193 receiving upadacitinib 30 mg
  • By week 96, 69 (76%) of 91 patients receiving upadacitinib 15 mg and 104 (74%) of 141 of those receiving upadacitinib 30 mg were in clinical remission
  • The most common adverse events of special interest were hepatic disorder, lymphopenia, creatine phosphokinase elevation, serious infection, neutropenia, and herpes zoster
mNRI indicates modified non-responder imputation analysis response

My take: This study shows a good durable (3 year) response to upadacitinib treatment with both 15 mg and 30 mg dosing.

Related blog posts:

    When an Inflammatory Bowel Disease Diagnosis is Far Away

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    JF McLaughin et al. Clin Gastroenterol Hepatol 2025; 23: 825-834. Travel Time to Treating Center Is Associated With Diagnostic Delay in Pediatric Inflammatory Bowel Disease

    This was a cross-sectional study of newly diagnosed pediatric patients (n=869) with IBD at 22 United States sites from 2019 to 2022. 57% were diagnosed with CD, 34% with UC, and 4% with IBD-U.

    Key findings:

    • Overall, the mean time from symptom onset to diagnosis was 265.9 days
    • Factors associated with longer diagnosis time included CD vs UC (odds ratio [OR], 2.6), and longer travel time to clinic (>1 hour [OR, 1.7], >2 hours [OR, 1.8] each vs <30 minutes)
    • There was no association with race, ethnicity, birth country, gender, parent education, household income, insurance type, health literacy, and health system distrust

    The finding that there is a longer diagnostic delay with CD than UC is consistent with prior studies. The longer travel time has not been widely recognized as a factor associated with delayed diagnosis, though it has been associated with other negative outcomes like higher mortality with chronic liver disease.

    Regarding the lack of a negative impact from factors like race/ethnicity and income, my suspicion is that this is probably related to several factors:

    • Overall, the pediatric age group has a very high rate of being insured as most children without commercial insurance currently qualify for Medicaid. This helps improve access to needed/timely health care
    • A recent study showed that pediatric GI specialists do not have disparities in treatment compared to pediatric GI providers with an IBD focus; thus, pediatric specialists are more likely to minimize treatment delay (Treatment Disparities in Adult vs. Pediatric IBD Care Related to Provider Specialization)
    • Parents help limit diagnostic delay in their children

    My take: There are many places that are far away from pediatric specialists. This results in diagnostic delays.

    Related blog posts:

    Mai Khao Beach, Phuket, Thailand

    Cholangiocarcinoma Risk in Pediatric PSC-IBD Plus one

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    B Kaj‐Carbaidwala et al. J Pediatr Gastroenterol Nutr. 2025; 80:450–454. Determining the time to cholangiocarcinoma in pediatric‐onset PSC‐IBD

    Background: “Cholangiocarcinoma is a devastating disease, with up to 80% mortality and limited treatment options…A large retrospective cohort study reported that cholangiocarcinoma occurred in 1000 per 100,000 (1%) of children with PSC, with all occurring in children over 15 years of age and at a median of 6 years after the PSC diagnosis…Primary sclerosing cholangitis (PSC) is associated with a 400× increased risk of cholangiocarcinoma.”

    Methods: Review of n = 175 studies resulted in a cohort of n = 21 patients with pediatric‐onset PSC‐IBD‐cholangiocarcinoma

    Key findings:

    • The earliest diagnosis of cholangiocarcinoma was made at 14 years of age.
    • 14% of of patients with pediatric‐onset PSC/IBD developed cholangiocarcinoma within the first 6 months of the second diagnosis
    • 23% of patients with pediatric‐onset PSC/IBD developed cholangiocarcinoma within the first year of the second diagnosis
    • 38% of patients with pediatric‐onset PSC/IBD developed cholangiocarcinoma within the first 2 years.
    • 50% of patients with pediatric‐onset PSC/IBD developed cholangiocarcinoma within the first 7 years
    • 50% of patients were between 14 and 25 years old when diagnosed with cholangiocarcinoma

    Based on these data, the authors recommend screening for cholangiocarcinoma in this population of pediatric patients with IBD-PSC. Screening would include ultrasound or magnetic resonance cholangiopancreatography along with serum cancer antigen 19‐9 screening every 6–12 months. At the same time, the authors acknowledge limitations including a highly-selected patient population (selection bias) and relatively small number of patients. The absolute increase in risk for cholangiocarcinoma is not known. This study did not provide an estimate of the number of patients with IBD-PSC who develop cholangiocarcinoma; it only provides data on those with cholangiocarcinoma (thus no denominator to establish risk).

    My take: Children, particularly adolescents, with IBD-PSC are at increased risk for both cholangiocarcinoma and colorectal cancer. The optimal surveillance strategy is still unclear. However, particularly in adolescents, I would favor yearly ultrasound and CA 19-9 for cholangiocarcinoma along with a low threshold for frequent colonoscopy (see ESPGHAN guidelines below).

    Related blog posts:

    In the news: AP 5/4/25: Cuts have eliminated more than a dozen US government health-tracking programs “U.S. Health Secretary Robert F. Kennedy Jr.’s motto is “ Make America Healthy Again,” but government cuts could make it harder to know if that’s happening…..Among those terminated at the Centers for Disease Control and Prevention were experts tracking abortions, pregnancies, job-related injuries, lead poisonings, sexual violence and youth smoking, the AP found.”

    Anantara Resort, Mai Khao Phuket

    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.

    Infection Risks with Biologic Switches: Findings from Recent Study

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    Briefly noted: AJ Kruger et al. Clinical Gastroenterology and Hepatology 2025. Biologic switch timing and risk of infection in patients with ulcerative colitis/Crohn’s disease: a retrospective study

    Methods: This was a “real-world practice” retrospective study (2017-2022) with 11,992 adult patients who were newly initiating a biologic therapy for UC/CD. 1,293 patients underwent a biologic switch, 64.2% of which were considered an overlapping switch (OS).

    Key findings:

    • Adjusted incidence ratio IR) per 1,000 person years, for any infection, were comparable across switching groups. No significant differences in aHR of infections were found between OS and NOS [any infection aHR: 1.40, P=.17; serious infection aHR: 0.95, P=.93].

    My take (borrowed from authors): “Overlapping switches were common and not associated with an increased risk of serious infection versus non-overlapping biologics.” Thus, shortened washout periods appear to pose minimal safety risks to patients while improving UC/CD therapy management.

    Related blog posts:

    Bohicket Creek near Charleston, SC

    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..

    ACCURE Trial: Appendectomy As an Adjunct Ulcerative Colitis Treatment Plus One

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    YIZ Acherman, et al. The Lancet Gastroenterology & Hepatology, 2025. DOI: 10.1016/S2468-1253(25)00026-3. Open access! Appendicectomy plus standard medical therapy versus standard medical therapy alone for maintenance of remission in ulcerative colitis (ACCURE): a pragmatic, open-label, international, randomised trial

    Background: “An inverse association between appendicectomy and the development of ulcerative colitis was first reported in 1987, with subsequent case-control studies confirming this observation, and suggesting a possible role of the appendix in ulcerative colitis. In 2016, our research group did a systematic review and meta-analysis of available (case-control) studies. This analysis showed that previous appendicectomy was associated with a significantly reduced risk of developing ulcerative colitis, with an overall odds ratio of 0·39 (95% CI 0·29–0·52).”

    Methods:  Adult patients (n=197) with established ulcerative colitis who were in remission but had been treated for disease relapse within the preceding 12 months were randomly assigned (1:1) to undergo appendicectomy plus continued maintenance medical therapy (intervention group) or to continue maintenance medical therapy alone (control group). Approximately 25% of participants had pancolitis.

    Key findings:

    • The 1-year relapse rate was significantly lower in the appendicectomy group than in the control group (36 [36%] of 99 patients vs 55 [56%] of 98 patients; relative risk 0·65 [p=0·005; adjusted p=0·002). 
    Relapse Rate

    My take (borrowed from the authors): “The ACCURE trial is the first randomised controlled trial evaluating the clinical effectiveness of appendicectomy in maintaining remission in patients with ulcerative colitis without advanced medical therapy (ie, biologicals or small molecules). This trial shows that laparoscopic appendicectomy, in addition to standard medical therapy, significantly reduces the relapse rates within 1 year.”

    Also, NPR notes 5/5/25: NIH cuts baby ‘Safe to Sleep’ team. Here’s what parents should know

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    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.