Search

Background Upadacitinib (upa) is a novel selective JAK-1 inhibitor that has demonstrated efficacy in the treatment of moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD) and has received regulatory approval for UC. We report a large prospective real-world experience with upa in patients with UC. Methods We performed a prospective analysis of clinical outcomes during upa therapy in patients with UC using pre-determined follow-up intervals at weeks 0, 2, 4, and 8 as part of a formalized treatment protocol. We used the Simplified Clinical Colitis Activity Index (SCCAI), C-reactive protein (CRP) and fecal calprotectin (FCP). Clinically active disease was defined as SCCAI ≥ 3. Clinical response was defined as a decrease of ≥ 3 points from baseline SCCAI. Clinical remission was defined as SCAAI < 3. Corticosteroid free clinical remission (CSFR) was defined as those in clinical remission, not taking systemic corticosteroid at the specific time point. CRP normalization was defined as baseline elevated and then within the normal range for the lab used (Quest Diagnostics (Secaucus, New Jersey) ≤8 mg/L or UChicago Medicine ≤5 mg/L). FCP response and remission was assessed at three different cutoffs: less than 250 μg/g, 150 μg/g, and 50μg/g. Adverse events were recorded as treatment-related adverse events (AE) and serious adverse events (SAE). Results 55 patients with UC received ≥4 weeks of upa (Table 1). 100% had previously received anti-TNF therapy and 81.8% had received ≥2 advanced therapies (biologic, small molecule, calcineurin-inhibitor). At 4 and 8 weeks of treatment, 18/22 (81.8%) and 19/21 (90.5%) achieved clinical response and 17/22 (77.3%) and 17/21 (81.0%) achieved clinical remission, respectively (Table 2). Of those who were on steroids at baseline, 100% (7 of 7) achieved CSFR. Results were seen as early as week 2 with clinical remission rates of 36.0%. Mean SCCAI decreased from 5.3 (SD 3.6) at week 0 to 1.71 (SD 3.96) at week 8 (p = 150 μg/g at baseline, 33.3% (2/6) achieved FCP 5 at week 0, 60% (3/5) achieved CRP Conclusion In this large prospective real-world experience in medically-resistant patients with UC, we describe that upadacitinib is rapidly effective and safe, with remission rates that exceed those seen in the pivotal trial.

Background Upadacitinib (upa) is a novel selective JAK-1 inhibitor that has demonstrated efficacy in the treatment of moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD) and has received regulatory approval for UC. We report our prospective real-world experience with upadacitinib in patients with CD. Methods We performed a prospective analysis of clinical outcomes during upa therapy in patients with CD using pre-determined follow-up intervals at weeks 0, 2, 4, and 8 as part of a formalized treatment evaluation protocol at our institution. We used the Harvey Bradshaw Index (HBI), C-reactive protein (CRP) and fecal calprotectin (FCP). Clinically active disease was defined as HBI ≥5. Clinical response was defined as a decrease of ≥ 3 points from baseline HBI. Clinical remission was defined as HBI Results 47 patients with CD received ≥4 weeks of upa (Table 1). 100% had previously received anti-TNF therapy and 93.6% had received ≥2 advanced therapies (biologic, small molecule, calcineurin-inhibitor). At weeks 4 and 8, 16/21 (76.2%) and 12/16 (75.0%) achieved clinical response and 14/21 (66.7%) and 11/16 (68.8%) achieved clinical remission by 8 weeks, respectively (Table 2). Of those who were on steroids at baseline, 100% (5/5) achieved CSFR. Results were seen as early as week 2 with clinical remission rates of 52.6%. Mean HBI decreased from 6.7 (SD 4.6) at week 0 to 3.5 (3.7) at week 8 (Figure 1). Mean FCP decreased by 707.0 (SD 1026.0) μg/g at week 0 to 74.6 (SD 56.2) μg/g at week 8. Of those with FCP >150 μg/g at baseline, 100% (4/4) achieved FCP 5 mg/L at week 0, 80% (4/5) achieved CRP Conclusion In this large, prospective real-world experience in medically-resistant patients with CD, we describe that upadacitinib is rapidly effective and safe.

Background The development and availability of Janus kinus inhibitors (JAKinibs) for moderately to severely active ulcerative colitis (UC) provides new therapeutic options with both novel mechanisms and unique pharmacodynamic benefits. Tofacitinib (tofa) is a non-selective pan-JAKinib that received FDA approval for UC in 2018 and upadacitinib (upa) is a JAK-1 selective inhibitor, that received FDA approval for UC in 2022. It is unknown whether patients who do not respond to tofa will subsequently respond to upa. We report our real-world experience with upa in UC patients with primary or secondary non-response to tofa. Methods We performed a prospective analysis of clinical outcomes on upa in patients with UC and Crohn’s disease (CD) using pre-determined intervals at weeks 0, 2, 4, and 8 as part of a formalized treatment protocol at our institution. We used the SCCAI and HBI, as well as CRP and fecal calprotectin (FCP) to assess efficacy and recorded treatment-related adverse events and serious adverse events (AEs). Here we report our experience in patients treated with upa who have been previously treated with tofa. Results 26 patients (18=UC, 8=CD) with primary or secondary non-response to tofa received upa. (Table 1) In addition to tofa, all of these patients failed at least two biologics prior to upa treatment. In UC: by week 2 60% (6/10) achieved clinical response, and 40% (4/10) achieved clinical remission. By week 4 87.5% (7/8) achieved clinical remission, and 87.5% (6/8) achieved steroid-free remission; FCP decreased by a mean of 649.2 μg/g from baseline (+/- 772.7). At week 8: 100% (8/8) of patients achieved clinical response, 87.5% (7/8) achieved clinical remission, and of all of these (7/7) achieved steroid-free remission; FCP decreased by a mean of 180 μg/g (+/- 721.8) from baseline. One patient had follow-up to week 12 and continued to be in steroid-free remission. (Table 2) In CD: by week 2 2 of 2 patients achieved clinical remission, by week 4 3 of 3 were in clinical remission, 2 of 3 achieved steroid-free remission, and one patient had follow-up to week 8 and he remained in steroid-free remission. (Table 2). 6 patients experienced AEs, with the most common being acne (19.2%). No infections, MACE, or VTE occurred. Conclusion In this prospective real-world experience in medically-resistant patients with UC and CD who previously failed treatment with tofa and at least two biologics, we describe that upa is rapidly effective, inducing both clinical, steroid-free, and biochemical remission with no serious AEs.

Investigation was carried out during the years 2013-14 and 2014-15 at Department of Horticulture, Post Graduate Institute, Dr. Panjabrao Deshmukh Krishi Vidyapeeth, Akola to evaluate drying techniques and to find out suitable desiccant, for Dutch roses. Minimum dry flower weight (2.46, 2.39 and 2.42g), decrease in flower weight, diameter of dry flower, minimum reduction in diameter of flower was observed when half bloom stage flowers dried by embedding in silicagel as compared to tight bud stage for the same during both the years (2013-14 and 2014-15) and which was further confirmed in pooled result.A half bloom harvest stage flowers of Gold Strike dried by embedding in silicagel recorded maximum per cent loss of moisture (71.35,75.68 and 73.58 %), per cent reduction in diameter of flowers (13.58, 16.37 and 14.97 %), whereas it was found minimum in tight bud harvest stage flowers of a cultivar Bordo. Among two stages of harvest half bloom harvest stage flowers embedding in silicagel recorded maximum sensory scores for colour, texture and appearance of dried flowers.

A class of birth processes having a variety of practical applications in penetration of new services and products is considered. Typically, statistical inferences on these models are performed by means of simple error structures placed on the deterministic analogs of the underlying stochastic processes. Motivated by the poor performance of conventional estimation methods, the problem of estimating the parameters of these models is readdressed. We develop necessary formulae for performing the maximum likelihood estimation and weighted least squares estimation methods, and demonstrate their superiority through analyses of some real data and simulation studies.

Objective : Childhood autopsies occurring during January 1997 to December 1999 were reviewed.Method : Of the total 1,445 deaths autopsied, 441 (30.5%) were of pediatric patients.Result : Of these deaths, 70.3% occurred during neonatal period, 8.6% in infancy, and 21.1% in childhood. Birth asphyxia (57.7%) was the most frequent mode of death in the neonatal period. Infections (67.2%) predominantly accounted for infant and childhood mortality, those of respiratory tract (46.1%) being most frequent in infancy, early and mid childhood, and ent< fever in late childhood (33.3%). Descrepancy between ante-mortem and post-mortem diagnosis occurred in 29 cases (6.6%)Conclusion : Autopsy is an important clinical tool providing useful information to the physician. Few published reports are available on pediatric autopsies. This study aims to help in a better understanding of causes of deaths in neonates, infants and children.

Motivated by poor performance of standard estimation methods in our application, the problem of modeling the diffusion of a new service (or a product) is considered without the assumption of a homogeneous population. The model consists of a two-stage procedure where customers receive purchase occasions according to a conventional diffusion model and at each purchase occasion they buy according to a binary choice model. This approach permits explicit incorporation of individual customer demographics and product attributes, whence one can study changes in diffusion as a function of changes in product attributes, prices, advertising, and customer demographics. The model has provided excellent results in a number of applications including the one on fax penetration reported here. In our applications this approach has been useful in market segmentation, studying the effect of marketing strategies, and in evaluating the effects of new service features. A limited validation is carried out to judge the forecasting performance of the model used in the fax example. A simulation study is carried out to compare the proposed solution with the result obtained by fitting the Bass model to a set of market segments separately. The simulation indicates that the proposed approach substantially improves over the aggregate fitting.

The issue of creating overdispersion in a given one parameter one dimensional exponential family, by extending it to a two parameter exponential family with the same support, is considered. An easily verifiable sufficient condition for this is derived. It is shown that a large class of families satisfy this condition and that this class includes EFron's (1986) and Lindsay's (1986) family as special cases. This class is also closely related to Jorgensen's (1988) Exponential Dispersion Models. UMP unbiased tests for testing overdispersion are exhibited and it is shown that in this context Cox's overdispersion test is a special case. A graphical display is developed to select a family of the general class which should be used with a given set of data to overdisperse a given target one parameter family. Two real data illustrations are given. (KR)

Analytical Laboratory, Pharmacy Department, Faculty of Technology & Engineering, M. S. University of Baroda, Kalabhavan, Baroda-390 001 Manuscript received 8 December 1989, revised 28 June 1994, accepted 21 September 1994 The infrared spectroscopy has been used for characterisation of EOM, asphaltenes and crude oils of the Cambay basin. The functional groups of EOM, asphaltene and crude oil were characterised and extinction ratios at maximum wave numbers of the respective groups were calculated. On the basis of these data, the type of EOM, its evolution path and original organic matter of Cambay basin have been identified.

We give a family of simultaneous confidence bands for the regression line α + βX for all X under the random intercept regression model. These types of models frequently arise in engineering and econometrics. The shape of the bands is controlled by the user, so many possible bands are obtainable. As an illustration, an engineering application involving a wind tunnel test of an aircraft design is described. The approach used is generalized to the case of two or more regressor variables.

In this paper, we propose a flexible class of discrete choice models. These models are flexible in that members of this class can approximate any discrete choice model obtained from utility maximization. All members of this class are intuitively easy to understand, consistent with utility maximization and do not suffer from the “independence of irrelevant alternatives” problem. In addition, there are members of this class for which maximum likelihood is a feasible estimation method even when the number of alternatives and/or attributes is large. Furthermore, appropriateness of specific functional forms can be explored graphically. We examine the properties of this class intuitively, theoretically, and in an empirical example.

Patterns of customer purchases are often modeled as discrete behavioral events following some probability law. These stochastic models have been applied separately to the phenomena of product class purchase incidence and brand choice (conditional on the products being purchased). Most of these models are probability mixture models where the parameters of an individual customer model vary across the population according to some distribution. This paper proposes a simple model of purchase behavior at the individual level, Poisson (λ) product purchases and Bernoulli (p) brand choices, so that λ and p characterise each customer. However, λ and p may vary jointly across the population in an arbitrary fashion. Therefore, purchase incidence and brand choice are treated together making no assumptions about the dependence between them. This generality is obtained at the cost of efficiency but enables us to focus on the individual behavior. Estimators (with known asymptotic properties) are developed for predicting future purchasing behavior of individuals conditional on their past purchasing behavior. These predictions of future purchases, at brand and product levels, are of interest to marketing managers. For example, what is the expected number of brand (or product) purchases in period 2 for the group of customers that made x brand and n product purchases in period 1? Apart from the basic insights provided by such predictions, they are particularly useful in evaluating the impact of marketing efforts. The model and the estimation results are applied to a frequently purchased product and compared with other stochastic approaches. While this paper focuses on buying behavior, the model is applicable to accidents, direct mail purchases and other random events.

Dalal and Klein (1985) obtained an approximation to discrete choice probabilities. This note justifies the use of this approximation in a forecasting context, where the forecast is made for a choice set of alternatives different from that used to initially estimate the model.

Consider samples of size $n$ from each of $k$ symmetric populations, differing only in their location parameters. The decision problem is to select the best population--the one with the largest location parameter--with control on the probability of correct selection (PCS) whenever the largest parameter is at least $\Delta$ units larger than all others, and whenever the common error distribution belongs to a specified neighborhood of the standard normal. It is shown that, if the sample size $n$ is chosen according to a formula given herein, and Huber's $M$-estimate is applied to each of the $k$ samples with the population having the largest estimate being selected as best, that the PCS goal is achieved asymptotically (as $\Delta\downarrow 0$)--the procedure is robust. Moreover, no other selection procedure can achieve this goal asymptotically with a smaller sample size--the procedure is most economical. Comparisons with other procedures are given. These results are based on a uniform asymptotic normality theorem for Huber's $M$-estimate, contained herein.

Let $\tau$ be a prior distribution over the parameter space $\Theta$ for a given parametric model $P_\theta, \theta \in \Theta$. For the sample space $\mathscr{X}$ (over which $P_\theta$'s are probability measures) belonging to a general class of topological spaces, which include the usual Euclidean spaces, it is shown that this parametric Bayes model can be approximated by a nonparametric Bayes model of the form of a mixture of Dirichlet processes prior, so that (i) the nonparametric prior assigns most of its weight to neighborhoods of the parametric model, and (ii) the Bayes rule for the nonparametric model is close to the Bayes rule for the parametric model in the no-sample case. Moreover, any prior parametric or nonparametric, may be approximated arbitrarily closely by a prior which is a mixture of Dirichlet processes. These results have implications in Bayesian inference.