Should we Target Complete Endoscopic Healing in Patients with Acute Severe Ulcerative Colitis?

BACKGROUND: Achieving endoscopic healing is a recommended target in ulcerative colitis [UC]. However, little is known about desirable goals in patients with acute severe UC [ASUC]. Taking advantage of the long-term follow-up of clinical trial patients with steroid-refractory ASUC, the present analysis aimed to quantify the observed association between the Mayo endoscopic sub-score [MES], 0 or 1, at clinical trial end and patients' long-term disease outcome. METHODS: Patients in the prospective CYSIF clinical trial were included in the present analysis if they had achieved steroid-free clinical remission with an MES of 0 or 1 at the end of the trial, at day 98. Events during long-term follow-up had been retrospectively collected. The primary endpoint for this complementary analysis was the occurrence of an event, death or disease relapse [defined by recurrence of symptoms with need for a new systemic treatment or colectomy]. RESULTS: Forty-four patients were included in the present analysis. When censoring follow-up at 5 years, six and nine events were observed among 26 and 18 patients having an MES of 0 and 1, respectively. Survival without disease relapse at 1, 2 and 5 years was respectively 88 ±â€…6, 81 ±â€…8 and 77 ±â€…8% in patients with MES of 0, and 72 ±â€…11, 53 ±â€…12 and 46 ±â€…12% in those with MES of 1 [hazard ratio: 2.8; 95% confidence interval: 1.0-8.0; p = 0.042]. CONCLUSION: In a cohort of patients admitted for ASUC in whom clinical and endoscopic healing has been achieved with a second-line medical therapy, better survival without disease relapse was observed with complete endoscopic healing.

Hepatitis B prevalence and associated factors in adults presenting for infection screening in northern Thailand.

Background and aims: Hepatitis B is a leading cause of morbidity and mortality worldwide. In view of the World Health Organization 2030 targets, effective screening of chronic infection is crucial. We have assessed the prevalence and risk factors of hepatitis B surface antigen in adults presenting for screening. Methods: Free-of-charge and anonymous services for simultaneous hepatitis B, hepatitis C, human immunodeficiency virus and syphilis screening and counseling were provided in four facilities in northern Thailand. Analyses were performed separately in clients born before integration into the 1992 hepatitis B vaccine Thailand's Expanded Program on Immunization and in clients born afterwards. Results: Between October 2015 and August 2020, hepatitis B surface antigen prevalence was 7.2 % (185/2578) in clients born before 1992 (95 % confidence interval [CI] = 6.2%-8.2 %). In the multivariable analysis, characteristics independently associated with a higher risk of infection were being born male (adjusted odds ratio [aOR] = 1.49, 95 % CI = 1.10-2.01) and being part of a hill tribe (aOR = 1.65, 95 % CI = 1.01-2.70). Forty-two percent were unaware of their infection. In clients born in 1992 or afterwards, prevalence was 1.5 % (43/2933) (95 % CI = 1.1%-2.0 %) and characteristics independently associated with a higher risk were being born between 1992 and 1995 (aOR = 1.90, 95 % CI = 1.00-3.61), being born male (aOR = 2.60, 95 % CI = 1.34-5.07), being part of a hill tribe (aOR = 5.09, 95 % CI = 2.52-10.26) and having ever injected drugs (aOR = 4.33, 95 % CI = 1.23-15.24). Conclusions: Risk factor-based screening would miss many chronic hepatitis cases. Screening all adults once in their lifetime may be beneficial until the second generation of immunized infants have reached adult age.

Uptake, acceptability and interpretability of 3-in-1 rapid blood self-testing for HIV, hepatitis B and hepatitis C.

INTRODUCTION: Early diagnosis is key to achieving the goal of eliminating transmission of HIV and hepatitis B and C. We assessed the uptake, acceptability and interpretability of self-testing using a 3-in-1 rapid diagnostic test (RDT) in facility-based services. METHODS: Stand-alone testing services were provided free of charge to consenting individuals aged ≥15 years in five facilities in northern Thailand. Clients were invited to choose between self-testing by fingerprick or venepuncture by a healthcare worker (HCW). In each facility, several clients could simultaneously self-test in separate private areas using TriQuik™ (Genlantis, San Diego, CA, USA), a single immunochromatographic cassette detecting HIV-1/2 antibody, hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCAb). An interactive program on a tablet computer was developed to collect socio-demographic, behavioural and satisfaction data and provide information to guide the self-test process, including video instructions, results interpretation and a picture of the cassette for immediate remote review by the HCW. When the HCW interpreted an HIV self-test as positive, the HCW collected blood by venepuncture for immediate confirmation. RESULTS: Between October 2020 and April 2022, 4119 clients presented for testing for the first time as part of the project. Of them, 3462 (84.0%) opted for self-testing. Among self-testers, 1801 (52.0%) were born female, the median age was 27 years (interquartile range, 22-36), 661 (19.1%) belonged to at least one key population and 2124 (61.4%) had never been tested for HIV; 3329 (99.8% of those who answered) reported being "very satisfied" or "satisfied" with the testing process. The proportions of test results interpreted as positive by self-testers among those interpreted as positive by HCWs were 95% for HIV-1/2 antibody, 95% for HBsAg and 78% for HCAb. CONCLUSIONS: These proportions were higher than those observed in a previous study evaluating another 3-in-1 RDT for HIV, HBsAg and HCAb, possibly due to the use of video instructions instead of paper-based instructions, lower prevalence and co-infection rates, or lower percentages of clients with low education level. Multiplex self-testing simplified and streamlined the service delivery process and was well accepted. HCW assistance proved to be essential in a limited number of cases.

Chronic Kidney Disease in a Large National Human Immunodeficiency Virus Treatment Program.

Tenofovir disoproxil fumarate (TDF) is associated with a risk of chronic kidney disease (CKD), especially in Asian populations. Data from the Thai national health insurance system was used to assess CKD incidence in patients receiving antiretroviral therapy in real-world practice. We analyzed data from patients who initiated one of the following first-line regimens: zidovudine + lamivudine + nevirapine (AZT + 3TC + NVP); zidovudine + lamivudine + efavirenz (AZT + 3TC + EFV); tenofovir + lamivudine + nevirapine (TDF + 3TC + NVP); tenofovir + lamivudine/emtricitabine + efavirenz (TDF + 3TC/FTC + EFV); and tenofovir +lamivudine +lopinavir/ritonavir (TDF + 3TC + LPV/r). CKD was defined as glomerular filtration rate <60 mL/min/1.73 m2 for >3 months, or a confirmed 2010 WHO diagnosis (ICD-10 code N183, N184, or N185). Death competing risk survival regression models were used. Among 27,313 participants, with a median age of 36.8 years and median follow-up of 2.3 years, 245 patients (0.9%) were diagnosed with CKD (incidence 3.2 per 1000 patient-years; 95% CI 2.8−3.6). Compared with patients receiving AZT + 3TC + NVP, the risk of CKD measured by adjusted sub-distribution hazard ratio (aSHR) was 6.5 (95% CI 3.9−11.1) in patients on TDF + 3TC + LPV/r, 3.8 (95% CI 2.3−6.0) in TDF + 3TC + NVP, and 1.6 (95% CI 1.2−2.3) in TDF + 3TC/FTC + EFV. Among patients receiving TDF, compared with those receiving TDF + 3TC/FTC + EFV, the aSHR was 4.0 (95% CI 2.3−6.8) in TDF + 3TC + LPV/r and 2.3 (95% CI 1.4−3.6) in TDF + 3TC + NVP. TDF was associated with an increased risk of CKD, especially when combined with LPV/r or NVP.

Development of a New Index to Assess Small Bowel Inflammation Severity in Crohn's Disease Using Magnetic Resonance Enterography.

Background: The severity of small bowel (SB) inflammation in Crohn's disease (CD) patients is a key component of the therapeutic choice. We aimed to develop a SB-CD Magnetic Resonance Enterography (MRE) index of Inflammation Severity (CDMRIS). Methods: Each gastroenterologist/radiologist pair in 13 centers selected MREs from 6 patients with SB-CD stratified on their perceived MRE inflammation severity. The 78 blinded MREs were allocated through balanced incomplete block design per severity stratum to these 13 pairs for rating the presence/severity of 13 preselected items for each SB 20-cm diseased segment. Global inflammation severity was evaluated using a 100-cm visual analog scale. Reproducibility of recorded items was evaluated. The CDMRIS was determined through linear mixed modeling as a combination of the numbers of segments with lesions highly correlated to global inflammation severity. Results: Four hundred and forty-two readings were available. Global inflammation severity mean ± SD was 21.0 ± 16.2. The independent predictors explaining 54% of the global inflammation severity variance were the numbers of segments with T1 mild-moderate and severe intensity of enhancement, deep ulceration without fistula, comb sign, fistula, and abscess. Unbiased correlation between CDMRIS and global inflammation severity was 0.76. Conclusions: The CDMRIS is now available to evaluate the severity of SB-CD inflammation. External validation and sensitivity-to-change are mandatory next steps.

Validation and Update of the Lémann Index to Measure Cumulative Structural Bowel Damage in Crohn's Disease.

BACKGROUND & AIMS: The Lémann Index is a tool measuring cumulative structural bowel damage in Crohn's disease (CD). We reported on its validation and updating. METHODS: This was an international, multicenter, prospective, cross-sectional observational study. At each center, 10 inclusions, stratified by CD duration and location, were planned. For each patient, the digestive tract was divided into 4 organs, upper tract, small bowel, colon/rectum, anus, and subsequently into segments, explored systematically by magnetic resonance imaging and by endoscopies in relation to disease location. For each segment, investigators retrieved information on previous surgical procedures, identified predefined strictures and penetrating lesions of maximal severity (grades 1-3) at each organ investigational method (gastroenterologist and radiologist for magnetic resonance imaging), provided segmental damage evaluation ranging from 0.0 to 10.0 (complete resection). Organ resection-free cumulative damage evaluation was then calculated from the sum of segmental damages. Then investigators provided a 0-10 global damage evaluation from the 4-organ standardized cumulative damage evaluations. Simple linear regressions of investigator damage evaluations on their corresponding Lémann Index were studied, as well as calibration plots. Finally, updated Lémann Index was derived through multiple linear mixed models applied to combined development and validation samples. RESULTS: In 15 centers, 134 patients were included. Correlation coefficients between investigator damage evaluations and Lémann Indexes were >0.80. When analyzing data in 272 patients from both samples and 27 centers, the unbiased correlation estimates were 0.89, 0,97, 0,94, 0.81, and 0.91 for the 4 organs and globally, and stable when applied to one sample or the other. CONCLUSIONS: The updated Lémann Index is a well-established index to assess cumulative bowel damage in CD that can be used in epidemiological studies and disease modification trials.

Evolution of Endoscopic Lesions in Steroid-Refractory Acute Severe Ulcerative Colitis Responding to Infliximab or Cyclosporine.

BACKGROUND/AIMS: Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. METHODS: Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of 0. RESULTS: Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS ≥6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p = .004 and p=.04), for bleeding and ulceration/erosion than for vascular pattern at day 42 [63% and 65% vs. 33% (n=54); p<.001 for both] and at day 98 [78% and 92% vs. 56% (n = 50); p = .007 and p < .001]. Global endoscopic remission rates at day 98 were higher in patients treated with infliximab than with cyclosporine [73% vs. 25% (n = 26 and 24); p < .001]. CONCLUSION: In steroid-refractory ASUC patients responding to a second-line medical therapy, endoscopic remission process started with bleeding remission and was not achieved in half the patients at day 98 for vascular pattern. Infliximab provided a higher endoscopic remission rate than cyclosporine at day 98.

STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD.

BACKGROUND: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) has proposed treatment targets in 2015 for adult patients with inflammatory bowel disease (IBD). We aimed to update the original STRIDE statements for incorporating treatment targets in both adult and pediatric IBD. METHODS: Based on a systematic review of the literature and iterative surveys of 89 IOIBD members, recommendations were drafted and modified in 2 surveys and 2 voting rounds. Consensus was reached if ≥75% of participants scored the recommendation as 7 to 10 on a 10-point rating scale. RESULTS: In the systematic review, 11,278 manuscripts were screened, of which 435 were included. The first IOIBD survey identified the following targets as most important: clinical response and remission, endoscopic healing, and normalization of C-reactive protein/erythrocyte sedimentation rate and calprotectin. Fifteen recommendations were identified, of which 13 were endorsed. STRIDE-II confirmed STRIDE-I long-term targets of clinical remission and endoscopic healing and added absence of disability, restoration of quality of life, and normal growth in children. Symptomatic relief and normalization of serum and fecal markers have been determined as short-term targets. Transmural healing in Crohn's disease and histological healing in ulcerative colitis are not formal targets but should be assessed as measures of the remission depth. CONCLUSIONS: STRIDE-II encompasses evidence- and consensus-based recommendations for treat-to-target strategies in adults and children with IBD. This frameworkshould be adapted to individual patients and local resources to improve outcomes.

Appointment reminders to increase uptake of HIV retesting by at-risk individuals: a randomized controlled study in Thailand.

INTRODUCTION: Frequent HIV testing of at-risk individuals is crucial to detect and treat infections early and prevent transmissions. We assessed the effect of reminders on HIV retesting uptake. METHODS: The study was conducted within a programme involving four facilities providing free-of-charge HIV, syphilis and hepatitis B and C testing and counselling in northern Thailand. Individuals found HIV negative and identified at risk by counsellors were invited to participate in a three-arm, open-label, randomized, controlled trial comparing: (a) "No Appointment & No Reminder" (control arm); (b) "No Appointment but Reminder": short message service (SMS) sent 24 weeks after the enrolment visit to remind booking an appointment, and sent again one week later if no appointment was booked; and (c) "Appointment & Reminder": appointment scheduled during the enrolment visit and SMS sent one week before appointment to ask for confirmation; if no response: single call made within one business day. The primary endpoint was a HIV retest within seven months after the enrolment visit. The cost of each reminder strategy was calculated as the sum of the following costs in United States dollars (USD): time spent by participants, counsellors and hotline staff; phone calls made; and SMS sent. The target sample size was 217 participants per arm (651 overall). RESULTS: Between April and November 2017, 651 participants were randomized. The proportion presenting for HIV retesting within seven months was 11.2% (24/215) in the control arm, versus 19.3% (42/218) in "No Appointment but Reminder" (p = 0.023) and 36.7% (80/218) in "Appointment & Reminder" (p < 0.001). Differences in proportions compared to the control arm were respectively +8.1% (95% CI: +1.4% to +14.8%) and +25.5% (+17.9% to +33.2%). The incremental cost-effectiveness ratios of "No Appointment but Reminder" and "Appointment & Reminder" compared to the control arm were respectively USD 0.05 and USD 0.14 per participant for each 5% increase in HIV retesting uptake within seven months. CONCLUSIONS: Scheduling an appointment and sending a reminder one week before was a simple, easy-to-implement and affordable intervention that significantly increased HIV retesting uptake in these at-risk individuals. The personal phone call to clients probably contributed, and also improved service efficiency.

Impact of Counseling Methods on HIV Retesting Uptake in At-Risk Individuals: A Randomized Controlled Study.

Systematic face-to-face pre-HIV test counseling is costly and may discourage clients to present for regular testing. In a randomized, controlled, non-inferiority trial conducted in four facilities providing free-of-charge anonymous HIV testing in Thailand, participants received either: standard counseling according to national guidelines (reference); computer-assisted counseling: interactive counseling on a tablet computer followed by an invitation to ask questions to the counselor; or on-demand counseling: invitation to ask questions to the counselor. Primary endpoint was a HIV retest within 7 months after enrolment visit. Following the planned interim analysis, on-demand counseling was discontinued for futility. In the final analysis in 1036 HIV-uninfected at-risk participants, computer-assisted counseling was non-inferior to standard counseling and had similar acceptability and improvements in HIV knowledge and sexual risk behaviors; however, it significantly reduced the time spent by counselors on counseling. Implementation of pre-HIV test computer-assisted counseling may ease the burden on staff involved in HIV testing.

Recommended First-Line Antiretroviral Therapy Regimens and Risk of Diabetes Mellitus in HIV-Infected Adults in Resource-Limited Settings.

OBJECTIVE: The use of some antiretroviral drugs has been associated with a higher risk of diabetes mellitus (DM) in HIV-infected patients, but the risk associated with antiretroviral drug combinations remains unclear. We investigated the association between first-line antiretroviral therapy (ART) regimens, recommended by the World Health Organization (WHO) in 2016, and the risk of DM in adults. METHOD: We selected all HIV-infected adults within the Thai National AIDS Program who started a first-line ART regimen consisting the following between October 2006 and September 2013: zidovudine+lamivudine+nevirapine; tenofovir disoproxil fumarate (TDF)+lamivudine+nevirapine; zidovudine+lamivudine+efavirenz; TDF+lamivudine/emtricitabine+efavirenz; zidovudine+lamivudine+ritonavir-boosted lopinavir (LPV/r); or TDF+lamivudine+LPV/r. Diagnosis of DM was defined as having at least 2 of the following characteristics: fasting plasma glucose ≥126 mg/dl, 2010 WHO ICD-10 codes E11-E14, or prescription of antidiabetic drugs. To identify ART regimens associated with DM, we used competing risks regression models that considered mortality without DM as a competing event and adjusted for sex, age, pancreas disease, and stratified by groups defined by a score summarizing the propensity to receive a specific first-line ART regimen. RESULTS: Data from 35 710 adults (49.1% male; median age, 35.0 years; median follow-up, 2.0 years) were included. In the multivariable analysis with zidovudine+lamivudine+nevirapine as the reference group, a higher risk of DM was observed with TDF+lamivudine/emtricitabine+efavirenz (adjusted sub-distribution hazard ratio [aSHR], 1.6; 95% confidence interval [CI], 1.3-1.9), zidovudine+lamivudine+efavirenz (aSHR, 2.0; 95% CI, 1.7-2.3), and TDF+lamivudine+LPV/r (aSHR, 2.7; 95% CI, 1.9-3.9). CONCLUSIONS: Several of the WHO recommended ART regimens, particularly tenofovir + lamivudine +LPV/r and regimens containing efavirenz, may be associated with an increased risk of DM.

Long term renal function in Asian HIV-1 infected adults receiving tenofovir disoproxil fumarate without protease inhibitors.

OBJECTIVES: The risk of kidney dysfunction on the WHO recommended first line regimens containing tenofovir disoproxil fumarate (TDF) without protease inhibitors (PI) remains unclear in Asian patients, especially those with low body weight. METHODS: Using data collected in a multicenter clinical trial in Thailand and proportional hazard regression models, we compared the risk of a >25% estimated glomerular filtration rate (eGFR) reduction in HIV naïve patients initiating TDF or zidovudine (AZT) containing non-PI regimen. RESULTS: Of 640 patients included in the analysis, 461 (72%) received a TDF-containing regimen for a median 6.7 years and 179 (28%) an AZT-containing regimen for 6.5 years. The risk of a >25% eGFR reduction was not associated with treatment (HR 1.11, 95% CI 0.84-1.47, P = 0.46). In multivariate analysis, the risk of >25% eGFR reduction form baseline was associated with body weight at baseline (HR 2.12, 95% CI 1.48-3.02 for <48 kg patients and HR 1.64, 95% CI 1.20-2.25 for 48-59.9 kg patients, compared to those with >60 kg, P < 0.001) and hypertension (HR 4.03, 95% CI 2.0-8.0, P < 0.001). The effect of baseline weight on >25% eGFR reduction did not significantly vary with treatment (P = 0.27). CONCLUSIONS: The risk of eGFR reduction was not higher on TDF- versus AZT-based non-PI regimens. Although the risk of eGFR reduction was greater for patients of lower body weight, this risk was not significantly increased by TDF.

Approaches to Integrating Biomarkers Into Clinical Trials and Care Pathways as Targets for the Treatment of Inflammatory Bowel Diseases.

BACKGROUND & AIMS: There is no consensus on the best way to integrate biomarkers into inflammatory bowel disease (IBD) research and clinical practice. The International Organization for the Study of Inflammatory Bowel Disease aimed to outline biomarker definitions, categories, and operating properties required for their use in registration trials and clinical practice. Using fecal calprotectin as an example, we provide a framework for biomarker development and validation in patients with IBD. METHODS: We reviewed international society guidelines, regulatory agency guidance documents, and standardized reporting guidelines for biomarkers, in combination with publications on fecal calprotectin levels in patients with IBD. We assessed the validity of fecal calprotectin to serve as a surrogate biomarker of IBD activity and outlined a framework for further validation and development of biomarkers. RESULTS: No endpoints have been fully validated as surrogates of risk of disease complications; mucosal healing is the most valid endpoint used to determine risk of disease complications. Fecal level of calprotectin has not been validated as a biomarker for IBD activity because of lack of technical and clinical reliability, assessment of performance when used as a replacement for endoscopy, and assessment of responsiveness to changes in disease states. The level of fecal calprotectin can be used only as a prognostic factor for disease recurrence in patients in remission after medical or surgical treatment. CONCLUSIONS: We reviewed guidelines, regulatory documents, and publications to identify properties required for the development of biomarkers of IBD activity and areas in need of clarification from regulatory agencies and societies. We propose a path forward for research of biomarkers for IBD.

Intradermal rabies post-exposure prophylaxis can be abridged with no measurable impact on clinical outcome in Cambodia, 2003-2014.

Rabies causes 60,000 deaths worldwide annually. Rabies post-exposure prophylaxis is highly effective but often geographically and financially beyond reach in endemic developing countries. We conducted a retrospective study on clinical outcome at ≥6 months in 3318 Cambodians who received intradermal Vero cell vaccine post-exposure prophylaxis after a bite by a rabid or sick-looking but untested dog in 2003-2014. An external expert panel examined verbal autopsy reports to identify rabies deaths. 1739 (93.65%) persons bitten by rabid- and 1066 (72.96%) bitten by sick-looking but untested dogs were traced and 513 were lost to follow-up. Among the former, 1591 (91.49%) and 129 (7.42%) patients referred for 4+ and 3 post-exposure prophylaxis sessions, respectively. Three persons died of probable rabies so that the overall percentage of survival was 99.83% (95% exact confidence interval: 99.49-99.96%) in post-exposure prophylaxis recipients bitten by confirmed rabid dogs. No significant difference was found in survival among patients who received 3 vs. 4+ sessions (with or without rabies immunoglobin). The power of the study, however, was limited. The current four sessions/one month intradermal regimen can be reduced to a three sessions/one week at no detectable added risk to patients, with the limitation of study power at 49%. A clinical follow-up system should be adopted by rabies prevention centers, especially to monitor implementation of an abridged course. The Institut Pasteur in Cambodia regimen will improve vaccine equity by treating 33% more patients with available doses, reduce direct cost of vaccination, transportation and other indirect costs to vaccinees.

Incidence and clinical outcomes of diabetes mellitus in HIV-infected adults in Thailand: a retrospective cohort study.

BACKGROUND: Since 2005, Thailand has scaled up one of the largest antiretroviral treatment (ART) programs in South East Asia. Although diabetes mellitus (DM) incidence is increasing in low and middle-income countries, its burden and contributing factors in the HIV infected population are not well known. METHODS: Using the Thai National AIDS Program data over a period of 8-years, we identified patients diagnosed with DM based on the following records: 1) fasting plasma glucose equal to or greater than 126 mg/dl following the 2013 American Diabetes Association criteria or 2) diagnosis codes E11-E14 of the 2010 WHO International Classification of Diseases, or 3) anti-diabetic drugs. Incidence was the number of new cases divided by that of person-years of follow-up (PYFU). Competing risks survival regression, treating death without DM as a competing event, was used to identify factors associated with DM. The risk of death in patients diagnosed with DM was estimated using Cox regression models. RESULTS: Data of 763,666 PYFU from 199,707 patients (54.2% male; median age 36.2 years at registration with the program) were available and 8383 cases were diagnosed with DM, resulting in an incidence rate of 11.0 per 1000 PYFU. New DM diagnosis was more likely in men (adjusted sub-distribution hazard ratio 1.2), older patients (compared to patients 18 to 34 years old: 1.8 for 35 to 44; 3.0 for 45 to 59; 3.8 for ≥60), and if ART was initiated (1.3). In 2014, 1313 (16.6%) of 7905 diabetic patients had DM complications (11.5% microvascular complications and 6.9% macrovascular complications). Patients diagnosed with DM were at higher risk of death compared to the others. CONCLUSIONS: DM incidence was higher in this Thailand cohort of HIV infected adults than in the general population. Risk factors were similar to those in the general population, in addition to starting ART.

Defining Endoscopic Remission in Ileocolonic Crohn's Disease: Let's Start from Scratch.

Endoscopic remission is the cornerstone of drug development and the guidance for daily clinical practice in Crohn's disease [CD]. However, although scoring systems for endoscopic activity in CD have been available for more than three decades, no consensus exists on the definition of endoscopic remission. In this viewpoint we describe the shortcomings of the current definition of endoscopic remission in ileocolonic CD and the essential requirements for a newly developed endoscopic scoring tool for endoscopic remission in CD.

A predictive model for risk of early grade ≥ 3 infection in patients with multiple myeloma not eligible for transplant: analysis of the FIRST trial.

Infections are a major cause of death in patients with multiple myeloma. A post hoc analysis of the phase 3 FIRST trial was conducted to characterize treatment-emergent (TE) infections and study risk factors for TE grade ≥ 3 infection. The number of TE infections/month was highest during the first 4 months of treatment (defined as early infection). Of 1613 treated patients, 340 (21.1%) experienced TE grade ≥ 3 infections in the first 18 months and 56.2% of these patients experienced their first grade ≥ 3 infection in the first 4 months. Risk of early infection was similar regardless of treatment. Based on the analyses of data in 1378 patients through multivariate logistic regression, a predictive model of first TE grade ≥ 3 infection in the first 4 months retained Eastern Cooperative Oncology Group performance status and serum ß2-microglobulin, lactate dehydrogenase, and hemoglobin levels to define high- and low-risk groups showing significantly different rates of infection (24.0% vs. 7.0%, respectively; P < 0.0001). The predictive model was validated with data from three clinical trials. This predictive model of early TE grade ≥ 3 infection may be applied in the clinical setting to guide infection monitoring and strategies for infection prevention.

Efficacy of adalimumab in patients with Crohn's disease and symptomatic small bowel stricture: a multicentre, prospective, observational cohort (CREOLE) study.

OBJECTIVE: The efficacy of anti-tumour necrosis factors (anti-TNFs) in patients with Crohn's disease (CD) and symptomatic small bowel stricture (SSBS) is controversial. The aim of this study was to estimate the efficacy of adalimumab in these patients and to identify the factors predicting success. DESIGN: We performed a multicentre, prospective, observational cohort study in patients with CD and SSBS. The included patients underwent magnetic resonance enterography at baseline and subsequently received adalimumab. The primary endpoint was success at week 24, defined as adalimumab continuation without prohibited treatment (corticosteroids after the eight week following inclusion, other anti-TNFs), endoscopic dilation or bowel resection. The baseline factors independently associated with success were identified using a logistic regression model, leading to a simple prognostic score. Secondary endpoints were prolonged success after week 24 (still on adalimumab, without dilation nor surgery) and time to bowel resection in the whole cohort. RESULTS: From January 2010 to December 2011, 105 patients were screened and 97 were included. At week 24, 62/97 (64%) patients had achieved success. The prognostic score defined a good prognosis group with 43/49 successes, an intermediate prognosis group with 17/28 successes and a poor prognosis group with 1/16 successes. After a median follow-up time of 3.8 years, 45.7%±6.6% (proportion±SE) of patients who were in success at week 24 (ie, 29% of the whole cohort) were still in prolonged success at 4 years. Among the whole cohort, 50.7%±5.3% of patients did not undergo bowel resection 4 years after inclusion. CONCLUSIONS: A successful response to adalimumab was observed in about two-thirds of CD patients with SSBS and was prolonged in nearly half of them till the end of follow-up. More than half of the patients were free of surgery 4 years after treatment initiation. CLINICAL TRIAL REGISTRATION NUMBER: NCT01183403; Results.