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1.
Psychiatr Serv ; : appips20230312, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38616648

ABSTRACT

The mental and behavioral health workforce shortage has hindered access to care in the United States, resulting in long waitlists for persons who need behavioral health care. Global models for task sharing, combined with U.S.-led studies of nonspecialists delivering interventions for depression and anxiety, support the development of this workforce in a stepped care system. This Open Forum highlights an innovative effort in Washington State to initiate a bachelor's-level behavioral health support specialist curriculum leading to credentialing to expand the mental health workforce and improve access to care for people with depression and anxiety.

2.
Cell Rep ; 43(3): 113935, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38460129

ABSTRACT

Autophagy and ribonucleoprotein granules, such as P-bodies (PBs) and stress granules, represent vital stress responses to maintain cellular homeostasis. SQSTM1/p62 phase-separated droplets are known to play critical roles in selective autophagy; however, it is unknown whether p62 can exist as another form in addition to its autophagic droplets. Here, we found that, under stress conditions, including proteotoxicity, endotoxicity, and oxidation, autophagic p62 droplets are transformed to a type of enlarged PBs, termed p62-dependent P-bodies (pd-PBs). p62 phase separation is essential for the nucleation of pd-PBs. Mechanistically, pd-PBs are triggered by enhanced p62 droplet formation upon stress stimulation through the interactions between p62 and DDX6, a DEAD-box ATPase. Functionally, pd-PBs recruit the NLRP3 inflammasome adaptor ASC to assemble the NLRP3 inflammasome and induce inflammation-associated cytotoxicity. Our study shows that p62 droplet-to-PB transformation acts as a stress response to activate the NLRP3 inflammasome process, suggesting that persistent pd-PBs lead to NLRP3-dependent inflammation toxicity.


Subject(s)
Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Humans , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Sequestosome-1 Protein , Processing Bodies , Inflammation , Autophagy/physiology
3.
J Crohns Colitis ; 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38366352

ABSTRACT

BACKGROUND AND AIMS: The risk of intrahepatic cholestasis of pregnancy (ICP) is increased in thiopurine exposed pregnancies. Thiopurine 'shunting', with a 6-methylmecrcaptopurine (MMP) to 6-thioguanine (TGN) ratio of >11, progresses over pregnancy, and may promote ICP development. We aimed to explore the association between thiopurine exposure and ICP, including the hypothesized impact of thiopurine shunting, and identify risk minimization strategies. METHODS: This prospective multi-centre cohort study compared thiopurine and biologic monotherapy exposed pregnant participants. Disease activity and obstetric outcome data, thiopurine metabolites, bile acids and transaminases were obtained preconception, in each trimester, at delivery, and post-partum. Thiopurine dose management was at the discretion of the treating physician. RESULTS: 131 thiopurine and 147 biologic monotherapy exposed pregnancies were included. MMP/TGN ratio increased from preconception to third trimester (p<0.01), with approximately 25% of participants shunting in pregnancy. Second trimester split-dosing led to a decrease in the median MMP/TGN ratio from 18 (IQR 6-57) to 3 (IQR 2-3.5) at delivery (p=0.04). The risk of ICP was increased in thiopurine exposed pregnancies (6.7% (7/105) vs 0% (0/112), p<0.001), with all ICP cases occurring in the setting of antenatal thiopurine shunting. Thiopurine dose increases (RR 8.10 [95% CI 1.88-34.85] p=0.005) and shunting in third trimester (6.20 [1.21-30.73] p=0.028) and at delivery (14.18 [1.62-123.9] p=0.016) were associated with an increased risk of ICP. CONCLUSIONS: Thiopurine exposure is associated with an increased risk of ICP, particularly following dose increases antenatally and with shunting in late pregnancy. The latter may be effectively managed with split dosing, although further studies are warranted.

4.
Inflamm Bowel Dis ; 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38330216

ABSTRACT

BACKGROUND: Despite reassuring clinical safety data, thrombocytosis, anemia, lymphopenia, and liver function derangements have been observed in infants born to women with inflammatory bowel disease (IBD) treated with thiopurines and biologics. We aimed to define the prevalence, course, associations, and clinical impact of hematological and biochemical abnormalities in such infants. METHODS: This multicenter prospective cohort study assessed clinical, hematologic, and biochemical outcomes of infants exposed to thiopurines or biologics in utero for management of maternal IBD. Liver transaminases, full blood examination, and infant thiopurine metabolites (where exposed) were taken at delivery and 6 weeks of age. Abnormal results were repeated until normalization. Infants were followed clinically by a pediatric gastroenterologist up to 2 years of age. RESULTS: A total of 130 infants were included. Thrombocytosis and elevated alanine transaminase (ALT) were seen in over half of infants up to 6 months of age with no significant clinical impact. Elevated ALT was associated with increasing maternal C-reactive protein in second trimester, while thrombocytosis was associated with increasing maternal C-reactive protein and fecal calprotectin in third trimester. Preceding infection and vaccination were associated with an increased risk of elevated alkaline phosphatase at 3 months. In those exposed to thiopurines, increasing maternal 6-methylmercaptopurine at delivery was associated with increased ALT to 6 months. CONCLUSIONS: Infants born to women with IBD commonly developed thrombocytosis, elevated alkaline phosphatase, and elevated ALT. These findings were associated with exposure to maternal inflammation, elevated 6-methylmercaptopurine at delivery, and infant vaccinations and infections, and had minimal clinical consequence.


Hematological and biochemical abnormalities have been observed in infants born to women with inflammatory bowel disease. This prospective study shows that thrombocytosis and elevated alanine transaminase are common in infants to 6 months of age and are associated with maternal inflammation, rather than with in utero medication exposures.

5.
J Comput Assist Tomogr ; 48(2): 257-262, 2024.
Article in English | MEDLINE | ID: mdl-38271533

ABSTRACT

OBJECTIVE: Computed tomography pulmonary angiogram (CTPA) is important to evaluate suspected pulmonary embolism in pregnancy but has maternal/fetal radiation risks. The objective of this study was to estimate maternal and fetal radiation-induced cancer risk from CTPA during pregnancy. METHODS: Simulation modeling via the National Cancer Institute's Radiation Risk Assessment Tool was used to estimate excess cancer risks from 17 organ doses from CTPA during pregnancy, with doses determined by a radiation dose indexing monitoring system. Organ doses were obtained from a radiation dose indexing monitoring system. Maternal and fetal cancer risks per 100,000 were calculated for male and female fetuses and several maternal ages. RESULTS: The 534 CTPA examinations had top 3 maternal organ doses to the breast, lung, and stomach of 17.34, 15.53, and 9.43 mSv, respectively, with a mean uterine dose of 0.21 mSv. The total maternal excess risks of developing cancer per 100,000 were 181, 151, 121, 107, 94.5, 84, and 74.4, respectively, for a 20-, 25-, 30-, 35-, 40-, 45-, and 50-year-old woman undergoing CTPA, compared with baseline cancer risks of 41,408 for 20-year-old patients. The total fetal excess risks of developing cancer per 100,000 were 12.3 and 7.3 for female and male fetuses, respectively, when compared with baseline cancer risks of 41,227 and 48,291. DISCUSSION: Excess risk of developing cancer from CTPA was small relative to baseline cancer risk for pregnant patients and fetuses, decreased for pregnant patients with increasing maternal age, and was greater for female fetuses than male fetuses.


Subject(s)
Neoplasms, Radiation-Induced , Pulmonary Embolism , Adult , Female , Humans , Male , Pregnancy , Young Adult , Angiography , Computed Tomography Angiography/adverse effects , Computed Tomography Angiography/methods , Delivery of Health Care , Fetus , Lung , Neoplasms, Radiation-Induced/epidemiology , Neoplasms, Radiation-Induced/etiology , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/epidemiology , Radiation Dosage , Retrospective Studies , Middle Aged
6.
Intern Med J ; 54(3): 446-454, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37255273

ABSTRACT

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of malignancy and infection compared to the general population. AIMS: We aim to identify risk factors for malignancy or serious infection in our IBD cohort. METHODS: Patients with IBD from a single tertiary referral centre were included. Demographic and clinical details, including immunosuppressant exposure, were collected and medical records retrospectively screened for adverse events, including malignancy or infection requiring hospitalisation. Logistic regression was used to evaluate risk factors for adverse events. RESULTS: Five hundred and forty-nine patients with IBD (340 Crohn disease (CD) and 209 ulcerative colitis (UC)) were studied. Forty-eight malignancies, including 39 (81.3%) non-melanoma skin cancers, 3 (6.3%) haematologic malignancies and 6 (15.4%) solid-organ malignancies, were identified, and 92 cases of serious infection were detected. IBD duration (odds ratio (OR) = 1.08; 95% confidence interval (CI) = 1.03-1.13) and ileocolonic CD (OR = 4.96; 95% CI = 1.13-21.71) were associated with increased odds of overall cancer. Compared with patients not previously exposed to the given class of immunosuppression assessed, the development of overall malignancy was not higher with thiopurine exposure (OR = 1.00; 95% CI = 0.50-2.24) or anti-tumour necrosis factor-alpha (TNF-α) exposure (OR = 0.78; 95% CI = 0.37-1.64). Similarly, compared with patients not exposed, infection risk was not affected by thiopurine (OR = 0.74; 95% CI = 0.46-1.20) or anti-TNF exposure (OR = 0.60; 95% CI = 0.38-0.95). CONCLUSIONS: Factors including ileocolonic CD and increasing IBD duration were associated with higher malignancy risk in this cohort. Compared with non-exposure, patients exposed to thiopurines were not at increased risk of malignancy or serious infection. Similarly, patients exposed to anti-TNF treatment did not experience increased rates of malignancy or serious infection compared to patients not exposed to this treatment.


Subject(s)
Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Neoplasms , Purines , Sulfhydryl Compounds , Humans , Retrospective Studies , Tumor Necrosis Factor Inhibitors , Inflammatory Bowel Diseases/drug therapy , Neoplasms/epidemiology , Colitis, Ulcerative/epidemiology , Crohn Disease/drug therapy , Risk Factors
7.
Endosc Int Open ; 11(12): E1161-E1167, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38094028

ABSTRACT

Background and study aims Foreign body ingestion is a common cause for Emergency Department presentation. In adults, foreign body ingestion is more common in patients with underlying psychiatric comorbidity, the elderly, alcohol intoxication, and in prisoners. This study reviewed the management of patients presenting to a tertiary hospital with foreign body ingestion. Patients and methods A retrospective review of patients presenting with foreign body ingestion to a tertiary hospital in Melbourne, Victoria, was undertaken from January 2017 to December 2021. Data collected included patient demographics, type of foreign body, length of stay, imaging modalities, management strategies, and complications. High-risk ingestion was defined as sharp objects, length >5 cm, diameter >2.5 cm, button battery and/or magnet ingestion or esophageal as per international guidelines. Results A total of 157 presentations by 63 patients with foreign body ingestion occurred between 2017 and 2021 (50% male; median age 30 years). Of the patients, 56% had underlying psychiatric comorbidities. The majority of presentations occurred in prisoners (65%). The most commonly ingested objects were batteries (23%), alleged drug-containing balloons (17%), razor blades (16%), and miscellaneous (40%). High-risk ingestion occurred in approximately two-thirds of presentations. Conservative management was the most common approach in 55% of patients. Complications, defined as perforation, bowel obstruction or fistula formation, did not occur in this cohort despite more than half presenting with high-risk ingestions. Thirty-day re-presentation rates were high (31%) and that was most common in patients with intentional ingestion, underlying mental health disorders, and a documented history of self-harm. Conclusions Conservative management for patients presenting with recurrent high-risk foreign body ingestion was safe in appropriately selected cases. Re-presentation is common and poses significant challenges for health care providers.

8.
bioRxiv ; 2023 Aug 28.
Article in English | MEDLINE | ID: mdl-37693536

ABSTRACT

Chemical probes interrogate disease mechanisms at the molecular level by linking genetic changes to observable traits. However, comprehensive chemical screens in diverse biological models are impractical. To address this challenge, we developed ChemProbe, a model that predicts cellular sensitivity to hundreds of molecular probes and drugs by learning to combine transcriptomes and chemical structures. Using ChemProbe, we inferred the chemical sensitivity of cancer cell lines and tumor samples and analyzed how the model makes predictions. We retrospectively evaluated drug response predictions for precision breast cancer treatment and prospectively validated chemical sensitivity predictions in new cellular models, including a genetically modified cell line. Our model interpretation analysis identified transcriptome features reflecting compound targets and protein network modules, identifying genes that drive ferroptosis. ChemProbe is an interpretable in silico screening tool that allows researchers to measure cellular response to diverse compounds, facilitating research into molecular mechanisms of chemical sensitivity.

9.
Inflamm Bowel Dis ; 2023 Aug 29.
Article in English | MEDLINE | ID: mdl-37643766

ABSTRACT

BACKGROUND: Inflammatory bowel disease (IBD) is best managed by a multidisciplinary team within a dedicated IBD service. IBD nurses play an important role within this team. We aimed to evaluate the contribution of our comprehensive outpatient IBD nursing service on patient outcomes, quality of care, and healthcare costs. METHODS: We performed a retrospective review of all IBD nurse encounters with patients over a 12-month period from October 2020 to September 2021 at a tertiary IBD referral center. Each nurse encounter was classified with respect to its clinical context, activities, and outcomes. Descriptive statistics were used to characterize these encounters and an economic analysis was performed to estimate the cost savings to the hospital. RESULTS: A total of 2537 nurse encounters occurred with 682 patients; 41% of encounters were nurse-initiated contacts with patients and 34% were patient-initiated contacts with the nurse helpline (26% via email, 8% via telephone). Most encounters involved clinical assessments (66%), providing education, counseling or updates (47%), and reviewing investigation results (38%). A gastroenterologist was consulted for advice in 35% of contacts. An estimated 29 emergency department visits, 1925 outpatient clinic visits, and 137 general practitioner visits were avoided. After deducting costs incurred, a net estimated annual saving of up to AUD $570 838 was achieved. Nurses commonly facilitated faster access to investigations (29%), education provision (28%), delivery of biologic services (25%), and medication changes (19%). CONCLUSIONS: A comprehensive IBD nursing service is associated with improved patient outcomes and quality of care, and reduced healthcare costs. This study supports the expanding role of IBD nurses in a modern multidisciplinary IBD service and the need for greater funding and integration of IBD nurses into IBD services.

10.
ANZ J Surg ; 93(6): 1503-1509, 2023 06.
Article in English | MEDLINE | ID: mdl-37095321

ABSTRACT

BACKGROUND: In medically refractory Ulcerative Colitis (UC), proctocolectomy with ileoanal pouch procedure (IAPP) is the preferred continence-preserving surgical option. Functional outcomes post-surgery and long-term complication rates in the biologic era remain ambiguous. This review primarily aims to provide an update on these outcomes. Secondarily, risk factors associated with chronic pouchitis and pouch failure are explored. METHODS: Two online databases (MEDLINE and EMBASE) were searched on 4 October 2022 for English studies from 2011-present relating to long-term outcomes of IAPP in inflammatory bowel disease (IBD) patients. Adult patients with 12 month follow-up were included. Studies focused on 30-day post-operative outcomes, non-IBD patients or studies including less than 30 patients were excluded. RESULTS: Following screening and full-text review of 1094 studies, 49 were included. Median sample size was n = 282 (IQR: 116-519). Median incidences for chronic pouchitis and pouch failure were 17.1% (IQR: 12-23.6%) and 6.9% (IQR: 4.8-10.8%), respectively. Upon multivariate analysis, chronic pouchitis development was most significantly associated with pre-operative steroid use, pancolitis and extra-intestinal IBD manifestations, whilst pouch failure was most significantly associated with pre-operative diagnosis of Crohn's disease (compared to UC), peri-operative pelvic sepsis and anastomotic leak. Overall patient satisfaction was very high with four included studies reporting greater than 90% satisfaction rates. CONCLUSION: Long-term complications for IAPP were common. However, despite this, patient satisfaction post-IAPP was high. Up-to-date knowledge of complication rates and their risk factors improves pre-operative counselling, management planning and patient outcomes.


Subject(s)
Colitis, Ulcerative , Colonic Pouches , Inflammatory Bowel Diseases , Pouchitis , Proctocolectomy, Restorative , Adult , Humans , Pouchitis/etiology , Pouchitis/complications , Colonic Pouches/adverse effects , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/surgery , Proctocolectomy, Restorative/adverse effects , Proctocolectomy, Restorative/methods , Colitis, Ulcerative/surgery , Colitis, Ulcerative/complications , Postoperative Complications/etiology
11.
Cardiovasc Intervent Radiol ; 46(5): 600-609, 2023 May.
Article in English | MEDLINE | ID: mdl-37012392

ABSTRACT

PURPOSE: The OsteoCool Tumor Ablation Post-Market Study (OPuS One) was a prospective, multi-national, single-arm study to investigate safety and effectiveness of radiofrequency ablation (RFA) for palliation of painful lytic bone metastases with 12 months of follow-up. RFA has demonstrated effective palliation of osseous metastases in small clinical studies with short-term follow-up; however, a long-term assessment with robust subject numbers is lacking. MATERIALS AND METHODS: Prospective assessments were conducted at Baseline, 3 days, 1 week, and 1, 3, 6, and 12-months. Pain and quality of life were measured prior to RFA and postoperatively using the Brief Pain Inventory, European Quality of Life-5 Dimension, and European Organization for Research and Treatment of Cancer Care Quality of Life Questionnaire for palliative care. Radiation, chemotherapy and opioid usage, and related adverse events were collected. RESULTS: 206 subjects were treated with RFA at 15 institutions in OPuS One. Worst pain, average pain, pain interference and quality of life significantly improved at all visits starting 3 days post-RFA and sustained to 12 months (P < 0.0001). Post hoc analysis found neither systemic chemotherapy nor local radiation therapy at the index site of RFA influenced worst pain, average pain, or pain interference. Six subjects had device/procedure-related adverse events. CONCLUSION: RFA for lytic metastases provides rapid (within 3 days) and statistically significant pain and quality of life improvements with sustained long-term relief through 12 months and a high degree of safety, independent of radiation. LEVEL OF EVIDENCE: 2B, PROSPECTIVE, NON-RANDOMIZED, POST-MARKET STUDY: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Subject(s)
Bone Neoplasms , Catheter Ablation , Radiofrequency Ablation , Humans , Palliative Care/methods , Quality of Life , Prospective Studies , Treatment Outcome , Pain/surgery , Bone Neoplasms/radiotherapy , Bone Neoplasms/secondary , Radiofrequency Ablation/methods , Catheter Ablation/methods
12.
Intern Med J ; 53(12): 2231-2239, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36916208

ABSTRACT

BACKGROUND: In 2014, infliximab (IFX) was listed on the Australian Pharmaceutical Benefits Scheme for acute severe ulcerative colitis (ASUC) and is now the preferred option for medical salvage, superseding cyclosporin A (CsA). Optimal dosing schedules for IFX remain unknown. AIM: The authors aim to evaluate the effect of changing from predominantly CsA to almost exclusively IFX for the treatment of steroid-refractory ASUC on colectomy rates. METHODS: A retrospective review was performed of patients admitted with ASUC between 2012 and 2020. Patients were categorised into two groups according to year of presentation - either 'historical treatment' cohort (2012-2014), when CsA was primarily used, or 'contemporary treatment' cohort (2014-2020), when IFX was mostly prescribed, in either standard or intensive doses. RESULTS: One hundred thirty-nine patients were included; 37 in the historical treatment cohort and 102 in the contemporary treatment cohort. In the historical treatment cohort, 12 of 37 received salvage therapy and eight (67%) received CsA. In the contemporary treatment cohort, 49 of 102 patients received salvage therapy, 40 (82%) with IFX, of whom 22 (53%) received intensified doses. Colectomy rates were similar at 30 days, 6 months and 12 months between historical and contemporary treatment cohorts (14% vs 12% [P = 0.77], 19% vs 18% [P > 0.99],and 22% vs 18% [P = 0.63], respectively). Difference in 12-month colectomy rates between standard versus intensive IFX did not meet statistical significance (three of 21 [14%] vs nine of 22 [41%]. respectively; P = 0.09). CONCLUSION: There was no difference in 30-day, 6-month or 12-month colectomy rates between the historical treatment and contemporary treatment cohorts. The use of IFX, rather than CsA, even at intensified dosing, does not appear to reduce the colectomy rate observed in our patients.


Subject(s)
Colitis, Ulcerative , Humans , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/surgery , Australia , Infliximab/therapeutic use , Cyclosporine/therapeutic use , Retrospective Studies , Colectomy , Treatment Outcome
13.
J Emerg Med ; 64(3): 295-303, 2023 03.
Article in English | MEDLINE | ID: mdl-36932003

ABSTRACT

BACKGROUND: Imaging for diagnosis of suspected pulmonary embolism in pregnancy presents radiation concerns for patient and fetus. OBJECTIVES: Estimate the risks of radiation-induced breast cancer and childhood leukemia from common imaging techniques for the evaluation of suspected pulmonary embolism in pregnancy. METHODS: Breast and uterine absorbed doses for various imaging techniques were input into the National Cancer Institute Radiation Risk Assessment Tool to calculate risk of breast cancer for the patient and childhood leukemia for the fetus. Absorbed doses were obtained by synthesizing data from a recent systematic review and the International Commission on Radiological Protection. Primary outcomes were the estimated excess incidences of breast cancer and childhood leukemia per 100,000 exposures. RESULTS: Baseline incidences of breast cancer for a 30-year-old woman and childhood leukemia for a male fetus were 13,341 and 939, respectively. Excess incidences of breast cancer were 0.003 and 0.275 for a single and two-view chest radiograph, respectively, 9.53 and 20.6 for low- and full-dose computed tomography pulmonary angiography (CTPA), respectively, 0.616 and 2.54 for low- and full-dose perfusion scan, respectively, and 0.732 and 2.66 for low- and full-dose ventilation perfusion scan, respectively. Excess incidences of childhood leukemia were 0.004 and 0.007 for a single and two-view chest radiograph, respectively, 0.069 and 0.490 for low- and full-dose CTPA, respectively, 0.359 and 1.47 for low- and full-dose perfusion scan, respectively, and 0.856 and 1.97 for low- and full-dose ventilation perfusion scan, respectively. CONCLUSION: Excess cancer risks for all techniques were small relative to baseline cancer risks, with CTPA techniques carrying slightly higher risk of breast cancer for the patient and ventilation perfusion techniques a higher risk of childhood leukemia.


Subject(s)
Breast Neoplasms , Leukemia , Neoplasms, Radiation-Induced , Pulmonary Embolism , Female , Pregnancy , Male , Humans , Adult , Fetus
14.
Eur J Drug Metab Pharmacokinet ; 48(3): 271-279, 2023 May.
Article in English | MEDLINE | ID: mdl-36952135

ABSTRACT

BACKGROUND AND OBJECTIVES: The role of therapeutic drug monitoring for ustekinumab in the treatment of Crohn's disease has not been defined. This study aimed to explore the relationship of serum ustekinumab trough concentration (UTC) with clinical and biochemical disease outcomes in a real-world setting. METHODS: We performed a retrospective analysis of Crohn's disease patients treated at a single tertiary centre. Ustekinumab was given as a single intravenous induction dose, followed by maintenance subcutaneous injections every 4 to 8 weeks. Rates of clinical remission (Harvey-Bradshaw Index ≤ 4), biochemical remission (C-reactive protein < 5 mg/l and faecal calprotectin < 150 µg/g) and complete remission were assessed at baseline and at the time of UTC testing during maintenance therapy. The association between baseline variables and UTC was tested using linear regression. We also performed an external validation analysis of UTC cut-offs established in four previously published studies. RESULTS: This study included 43 patients. Compared to 8-weekly dosing, a 2.49- and 2.65-fold increase in UTC was associated with 6-weekly and 4-weekly dosing respectively. However, there was no significant difference in clinical, biochemical or complete remission among the dosing groups. An external validation of previously published optimal UTC cut-offs found low predictive value for our patient population. CONCLUSIONS: In this study, dosing interval was the only determinant significantly associated with a higher UTC for patients on maintenance ustekinumab therapy. While a higher UTC may be achieved with dose escalation, it was not associated with improved rates of clinical or biochemical response in our cohort.


Subject(s)
Crohn Disease , Ustekinumab , Humans , Adult , Ustekinumab/therapeutic use , Crohn Disease/drug therapy , Crohn Disease/metabolism , Retrospective Studies , Remission Induction , Administration, Intravenous
15.
Intern Med J ; 53(10): 1866-1874, 2023 10.
Article in English | MEDLINE | ID: mdl-36112394

ABSTRACT

BACKGROUNDS AND AIMS: Inflammatory bowel disease (IBD) affects a growing cohort of elderly patients. Our aim was to compare the quality of care received by elderly patients with IBD with a nonelderly adult IBD population using clinical markers including steroid-free clinical remission. METHOD: Retrospective audit of all consecutive patients attending a specialist IBD centre over a 1-year period aged >60 (elderly cohort [EC]) and 50 consecutive patients aged 30-45 years (control cohort [CC]). A follow-up survey was completed assessing current symptoms and perceptions of care. RESULTS: One hundred thirty-nine patients were evaluated (89 EC, 50 CC). Steroid-free clinical remission was observed less commonly in the EC (58, 64%) compared with the CC (40, 80%) (P < 0.05). Biologics such as infliximab (15% EC vs 36% CC; P < 0.01) and adalimumab (14% EC vs 30% CC; P = 0.02) were used less frequently in the EC, whilst vedolizumab (6% EC vs 6% CC; P = 1) and ustekinumab (3% EC vs 2% CC; P = 1) were used at a similar frequency. Patients in the EC were less likely to have specialist IBD nursing contact (P < 0.01), smoking screening (P < 0.011) or influenza vaccinations (P < 0.006). IBD nurse contact was associated with significantly greater provision of the preventative care measures. CONCLUSION: Elderly patients with IBD were less likely to experience steroid-free clinical remission or be prescribed biologics. Elderly patients were less likely to receive education with respect to preventative medicine. The models of care for the elderly need re-evaluation and greater incorporation with the multidisciplinary IBD team.


Subject(s)
Biological Products , Colitis, Ulcerative , Inflammatory Bowel Diseases , Adult , Aged , Humans , Colitis, Ulcerative/diagnosis , Retrospective Studies , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/epidemiology , Infliximab/therapeutic use , Biological Products/therapeutic use
16.
ACG Case Rep J ; 9(9): e00838, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36072354

ABSTRACT

Microscopic colitis is a form of colonic inflammation that presents with chronic nonbloody diarrhea that can only be diagnosed histologically with biopsies obtained during colonoscopy. We report a rare case of isotretinoin-induced microscopic colitis in a patient who was prescribed this medication for nodular acne with a 1-year history of nonbloody diarrhea, bloating, cramping, and foul-smelling gas. Cessation of this medication in addition to initiating treatment with budesonide resulted in remission of the patient's symptoms. The presence of chronic diarrhea in patients who are taking isotretinoin should raise suspicion for this condition and warrant further investigation.

17.
Endosc Int Open ; 10(7): E1004-E1013, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35845028

ABSTRACT

Background and aims Artificial intelligence (AI) technology is being evaluated for its potential to improve colonoscopic assessment of inflammatory bowel disease (IBD), particularly with computer-aided image classifiers. This review evaluates the clinical application and diagnostic test accuracy (DTA) of AI algorithms in colonoscopy for IBD. Methods A systematic review was performed on studies evaluating AI in colonoscopy of adult patients with IBD. MEDLINE, Embase, Emcare, PsycINFO, CINAHL, Cochrane Library and Clinicaltrials.gov databases were searched on 28 th April 2021 for English language articles published between January 1, 2000 and April 28, 2021. Risk of bias and applicability were assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Diagnostic accuracy was presented as median (interquartile range). Results Of 1029 records screened, nine studies with 7813 patients were included for review. AI was used to predict endoscopic and histologic disease activity in ulcerative colitis, and differentiation of Crohn's disease from Behcet's disease and intestinal tuberculosis. DTA of AI algorithms ranged between 52-91 %. The sensitivity and specificity for AI algorithms predicting endoscopic severity of disease were 78 % (range 72-83, interquartile range 5.5) and 91 % (range 86-96, interquartile range 5), respectively. Conclusions AI has been primarily used to assess disease activity in ulcerative colitis. The diagnostic performance is promising and suggests potential for other clinical application of AI in IBD colonoscopy such as dysplasia detection. However, current evidence is limited by retrospective data and models trained on still images only. Future prospective multicenter studies with full-motion videos are needed to replicate the real-world clinical setting.

19.
J Crohns Colitis ; 16(9): 1475-1492, 2022 Sep 08.
Article in English | MEDLINE | ID: mdl-35325076

ABSTRACT

BACKGROUND AND AIMS: Alterations in body composition are common in inflammatory bowel disease [IBD] and have been associated with differences in patient outcomes. We sought to consolidate knowledge on the impact and importance of body composition in IBD. METHODS: We performed a systematic search of MEDLINE, EMBASE and conference proceedings by combining two key research themes: inflammatory bowel disease and body composition. RESULTS: Fifty-five studies were included in this review. Thirty-one focused on the impact of IBD on body composition with a total of 2279 patients with a mean age 38.4 years. Of these, 1071 [47%] were male. In total, 1470 [64.5%] patients had Crohn's disease and 809 [35.5%] had ulcerative colitis. Notably, fat mass and fat-free mass were reduced, and higher rates of sarcopaenia were observed in those with active IBD compared with those in clinical remission and healthy controls. Twenty-four additional studies focused on the impact of derangements in body composition on IBD outcomes. Alterations in body composition in IBD are associated with poorer prognoses including higher rates of surgical intervention, post-operative complications and reduced muscle strength. In addition, higher rates of early treatment failure and primary non-response are seen in patients with myopaenia. CONCLUSIONS: Patients with IBD have alterations in body composition parameters in active disease and clinical remission. The impacts of body composition on disease outcome and therapy are broad and require further investigation. The augmentation of body composition parameters in the clinical setting has the potential to improve IBD outcomes in the future.


Subject(s)
Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Adult , Body Composition , Chronic Disease , Colitis, Ulcerative/complications , Colitis, Ulcerative/therapy , Crohn Disease/complications , Female , Humans , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/therapy , Male
20.
PLoS Comput Biol ; 18(1): e1009719, 2022 01.
Article in English | MEDLINE | ID: mdl-35100256

ABSTRACT

Artificial Intelligence (AI) has the power to improve our lives through a wide variety of applications, many of which fall into the healthcare space; however, a lack of diversity is contributing to limitations in how broadly AI can help people. The UCSF AI4ALL program was established in 2019 to address this issue by targeting high school students from underrepresented backgrounds in AI, giving them a chance to learn about AI with a focus on biomedicine, and promoting diversity and inclusion. In 2020, the UCSF AI4ALL three-week program was held entirely online due to the COVID-19 pandemic. Thus, students participated virtually to gain experience with AI, interact with diverse role models in AI, and learn about advancing health through AI. Specifically, they attended lectures in coding and AI, received an in-depth research experience through hands-on projects exploring COVID-19, and engaged in mentoring and personal development sessions with faculty, researchers, industry professionals, and undergraduate and graduate students, many of whom were women and from underrepresented racial and ethnic backgrounds. At the conclusion of the program, the students presented the results of their research projects at the final symposium. Comparison of pre- and post-program survey responses from students demonstrated that after the program, significantly more students were familiar with how to work with data and to evaluate and apply machine learning algorithms. There were also nominally significant increases in the students' knowing people in AI from historically underrepresented groups, feeling confident in discussing AI, and being aware of careers in AI. We found that we were able to engage young students in AI via our online training program and nurture greater diversity in AI. This work can guide AI training programs aspiring to engage and educate students entirely online, and motivate people in AI to strive towards increasing diversity and inclusion in this field.


Subject(s)
Artificial Intelligence , Biomedical Research , Computational Biology , Cultural Diversity , Mentoring , Adolescent , Biomedical Research/education , Biomedical Research/organization & administration , Computational Biology/education , Computational Biology/organization & administration , Female , Humans , Male , Minority Groups , Students
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