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1.
Dig Dis Sci ; 67(1): 252-258, 2022 01.
Article in English | MEDLINE | ID: mdl-33595782

ABSTRACT

BACKGROUND: Inflammatory bowel diseases (IBD) are often treated with anti-tumor necrosis factor alpha (anti-TNFα) medications. Concomitant treatment of IBD with anti-TNFα agents and immunomodulators appears to be associated with an increased risk for lymphoma. METHODS: Patients who developed lymphoma while on monotherapy with an anti-TNFα agent were identified at three centers. Institutional Review Board approval was obtained. RESULTS: Five adolescents and young adult patients with pediatric-onset IBD who were treated with infliximab (IFX) without exposure to thiopurines were subsequently diagnosed with lymphoma. Three of the five patients had bone involvement at presentation. Epstein-Barr virus was positive in 2 cases. Median time from diagnosis of IBD and exposure to IFX prior to diagnosis of lymphoma was 5 and 4.3 years, respectively. CONCLUSIONS: This case series reports long-term follow-up for young patients with IBD who were treated with IFX monotherapy and developed lymphoma. Three of the five patients had bone involvement. In general, the risk of lymphoma following exposure to anti-TNFα medications alone remains low, but the incidence of primary bone lymphomas in IBD has not been reported. Studies examining longer exposure times may be needed to determine the true lymphoma risk in patients treated with IFX monotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Colitis, Ulcerative , Crohn Disease , Drug Substitution/methods , Infliximab , Lymphoma , Adolescent , Age of Onset , Bone and Bones/diagnostic imaging , Bone and Bones/pathology , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/epidemiology , Crohn Disease/drug therapy , Crohn Disease/epidemiology , Female , Herpesvirus 4, Human/isolation & purification , Humans , Infliximab/administration & dosage , Infliximab/adverse effects , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Lymphoma/diagnosis , Lymphoma/etiology , Lymphoma/physiopathology , Lymphoma/therapy , Male , Treatment Outcome , Tumor Necrosis Factor Inhibitors/administration & dosage , Tumor Necrosis Factor Inhibitors/adverse effects , Young Adult
2.
Expert Opin Biol Ther ; 20(4): 429-435, 2020 04.
Article in English | MEDLINE | ID: mdl-31652087

ABSTRACT

Introduction: More extensive disease, high rates of corticosteroid refractory and dependent disease, and the potential impact of disease on growth and development differentiate inflammatory bowel disease in children from adults. This is particularly evident in ulcerative colitis where pancolitis predominates, success of mesalamine alone in achieving remission is less than 50%, and there is a high need for immunomodulator or biologic therapies.Areas Covered: This review describes the use of infliximab, adalimumab, golimumab, and vedolizumab in the treatment of children with ulcerative colitis but is limited in scope due to the paucity of controlled clinical trials. A search of existing literature with keywords of these specific biological therapies as well as 'pediatric', 'ulcerative colitis,' and 'inflammatory bowel disease' was used to complete this review.Expert Opinion: Therapeutic drug monitoring has become standard of care when assessing dosing and changes in therapy and will play a role in future treatment planning.


Subject(s)
Biological Products/therapeutic use , Colitis, Ulcerative/drug therapy , Adalimumab/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Child , Drug Therapy, Combination , Humans , Infliximab/therapeutic use , Tumor Necrosis Factor-alpha/immunology , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/therapeutic use
3.
Science ; 360(6391): 915-918, 2018 05 25.
Article in English | MEDLINE | ID: mdl-29798884

ABSTRACT

Biomolecular monitoring in the gastrointestinal tract could offer rapid, precise disease detection and management but is impeded by access to the remote and complex environment. Here, we present an ingestible micro-bio-electronic device (IMBED) for in situ biomolecular detection based on environmentally resilient biosensor bacteria and miniaturized luminescence readout electronics that wirelessly communicate with an external device. As a proof of concept, we engineer heme-sensitive probiotic biosensors and demonstrate accurate diagnosis of gastrointestinal bleeding in swine. Additionally, we integrate alternative biosensors to demonstrate modularity and extensibility of the detection platform. IMBEDs enable new opportunities for gastrointestinal biomarker discovery and could transform the management and diagnosis of gastrointestinal disease.


Subject(s)
Biosensing Techniques/instrumentation , Gastrointestinal Diseases/diagnosis , Gastrointestinal Tract/microbiology , Gastrointestinal Tract/physiopathology , Monitoring, Physiologic/instrumentation , Probiotics , Animals , Electrical Equipment and Supplies , Gastrointestinal Diseases/microbiology , Gastrointestinal Hemorrhage/diagnosis , Heme/chemistry , Swine
4.
PLoS One ; 8(6): e65653, 2013.
Article in English | MEDLINE | ID: mdl-23762406

ABSTRACT

BACKGROUND: HIV drug resistance (HIVDR) testing is not routinely available in many resource-limited settings, therefore antiretroviral therapy (ART) program and site factors known to be associated with emergence of HIVDR should be monitored to optimize the quality of patient care and minimize the emergence of preventable HIVDR. METHODS: In 2010, Namibia selected five World Health Organization Early Warning Indicators (EWIs) and scaled-up monitoring from 9 to 33 ART sites: ART prescribing practices, Patients lost to follow-up (LTFU) at 12 months, Patients switched to a second-line regimen at 12 months, On-time antiretroviral (ARV) drug pick-up, and ARV drug-supply continuity. RESULTS: Records allowed reporting on three of the five selected EWIs. 22 of 33 (67%) sites met the target of 100% initiated on appropriate first-line regimens. 17 of 33 (52%) sites met the target of ≤20% LTFU. 15 of 33 (45%) sites met the target of 0% switched to a second-line regimen. CONCLUSIONS: EWI monitoring directly resulted in public health action which will optimize the quality of care, specifically the strengthening of ART record systems, engagement of ART sites, and operational research for improved adherence assessment and ART patient defaulter tracing.


Subject(s)
Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , Drug Resistance, Viral/drug effects , HIV Infections/drug therapy , HIV Infections/virology , Health Status Indicators , Public Health , Anti-HIV Agents/supply & distribution , Antiretroviral Therapy, Highly Active , Geography , Humans , Lost to Follow-Up , Namibia , Practice Patterns, Physicians' , World Health Organization
5.
PLoS One ; 8(2): e56307, 2013.
Article in English | MEDLINE | ID: mdl-23509605

ABSTRACT

The visual-analogue scale (VAS), Likert item (rating scale), pills identification test (PIT), and medication possession ratio (MPR) provide estimates of antiretroviral therapy (ART) adherence which correlate with HIV viral suppression. These simple adherence measures are inexpensive and easy to administer; however, require validation and adjustment prior to implementation. The objective of this study was to define the optimal adherence assessment measure in Namibia to identify patients at risk for sub-optimal adherence and poor virologic response 6 months after ART initiation. We conducted a cross-sectional survey in HIV-infected adults receiving ART for 6-12 months prior to the adherence assessment. Adherence measures included 30-day VAS, 30-day Likert item, self-reported treatment interruptions, PIT, and MPR. Association of adherence measures with 6-month HIV-1 RNA level was assessed using two thresholds (1000 copies/mL and 5000 copies/mL). Adherence was assessed in 236 patients, mean age 37.3 years, 54% female. Mean adherence was 98.1% by 30-day VAS, 84.7% by 30-day Likert item, 97.0% by self-reported treatment interruptions, 90.6% by PIT, and 98.8% by MPR. Agreement between adherence measures was poor using kappa statistic. 76% had HIV-1 RNA <1000 copies/ml, and 88% had HIV-1 RNA <5000 copies/ml. MPR (continuous) was associated with viral suppression <5000 copies/ml (p = 0.036). MPR <75% was associated with virologic failure at ≥5000 copies/ml with OR 3.89 (1.24, 12.21), p = 0.013. Adherence was high with all measures. Only MPR, was associated with short-term virologic response, suggesting its cross-culturally utility for early identification of patients at high risk for virologic failure.


Subject(s)
Antiretroviral Therapy, Highly Active/statistics & numerical data , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV-1/genetics , Patient Compliance/statistics & numerical data , Adult , Cross-Sectional Studies , Female , Humans , Male , Namibia/epidemiology , RNA, Viral/analysis
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