Estimating the undetected infections in the Monkeypox outbreak.

While the number of detected Monkeypox infections are widely available, an understanding of the extent of undetected cases is urgently needed for an effective tackling of its spread. The aim of this study is to estimate the true number of Monkeypox (detected and undetected) infections in most affected countries. The question being asked is: How many cases have actually occurred? We propose a lower bound estimator for the true number of Monkeypox cases. The estimator is data-driven and can be easily computed from the cumulative distributions of weekly cases. We focused on the ratio of the total estimated cases to the observed cases on July 31, 2022: The proportion of undetected cases was relevant in all countries, with countries whose estimated true number of infections could be more than three times the observed one. We provided a practical contribution to the understanding of the current Monkeypox wave and reliable estimates on how many undetected cases are going around in several countries, where the epidemic spreads differently.

Natural History of Ulcerative Colitis with Coexistent Colonic Diverticulosis.

Ulcerative colitis (UC) and colonic diverticulosis can co-exist in some patients. However, the natural history of UC associated with colonic diverticulosis is not well known. We here compared the disease characteristics and outcome of UC patients with and without concomitant colonic diverticulosis. Medical records of 347 UC patients were included in an observational, retrospective, nested-matched case-control study. Cases were 92 patients with UC and concomitant colonic diverticulosis, while controls were 255 UC patients without concomitant colonic diverticulosis. A propensity score matching (PSM) was used to homogenate cases (n = 92) and controls (n = 153) for age. UC patients with concomitant colonic diverticulosis were less likely to have an extensive disease (25/92, 27.1%) and to experience steroid dependence (8/92, 8.6%) compared to patients without concomitant colonic diverticulosis (70/153, 45.7% and 48/153, 31.3%, respectively; p < 0.001). The use of immunosuppressants (9/92, 9.7% vs. 37/153, 24.1%; p = 0.007) or biologics (3/92, 3.2% vs. 26/153, 16.9%, p < 0.001) was significantly lower in UC patients with concomitant diverticulosis compared to the control group. On multivariate analysis, steroid dependence and extensive colitis were significantly less frequent in UC patients with concomitant colonic diverticulosis compared to UC patients without diverticula. UC patients with coexisting colonic diverticulosis are less likely to have an extensive disease and to be steroid-dependent.

Upper bound estimators of the population size based on ordinal models for capture-recapture experiments.

Capture-recapture studies have attracted a lot of attention over the past few decades, especially in applied disciplines where a direct estimate for the size of a population of interest is not available. Epidemiology, ecology, public health, and biodiversity are just a few examples. The estimation of the number of unseen units has been a challenge for theoretical statisticians, and considerable progress has been made in providing lower bound estimators for the population size. In fact, it is well known that consistent estimators for this cannot be provided in the very general case. Considering a case where capture-recapture studies are summarized by a frequency of frequencies distribution, we derive a simple upper bound of the population size based on the cumulative distribution function. We introduce two estimators of this bound, without any specific parametric assumption on the distribution of the observed frequency counts. The behavior of the proposed estimators is investigated using several benchmark datasets and a large-scale simulation experiment based on the scheme discussed by Pledger.

Effect of Vedolizumab on Anemia of Chronic Disease in Patients with Inflammatory Bowel Diseases.

BACKGROUND: Anemia of Chronic Disease (ACD) can negatively influence the clinical course of Inflammatory Bowel Disease (IBD) patients. The aim of this study was to evaluate the effect of Vedolizumab on ACD in IBD. METHODS: Clinical data of 75 IBD patients (25 Crohn's disease (CD) and 50 Ulcerative Colitis (UC)) receiving Vedolizumab in a tertiary referral IBD center were retrospectively evaluated and the effect of the drug on ACD was ascertained at weeks 14 and 24. RESULTS: ACD was diagnosed in 35 (11 CD and 24 UC) out of 75 (47%) IBD patients. At both week 14 and week 24, improvements and resolutions of ACD were achieved by 13/35 (37%) and 11/35 (31%) patients, respectively. Baseline demographic/clinical characteristics did not differ between patients with ACD improvements/resolutions and those with persistent ACD. Clinical response occurred more frequently in patients who achieved ACD resolution (10/11, 91%) than in those without ACD improvement (5/11, 45%, p = 0.022). When analysis was restricted to anemic patients, ACD resolution was documented in 10/22 patients (45%) achieving clinical response and 1/13 of non-responders (8%; p = 0.02). CONCLUSIONS: ACD occurs in half of the IBD patients and, in nearly two thirds of them, Vedolizumab treatment associates with ACD resolution/improvement.

Estimating the undetected infections in the Covid-19 outbreak by harnessing capture-recapture methods.

OBJECTIVES: A major open question, affecting the decisions of policy makers, is the estimation of the true number of Covid-19 infections. Most of them are undetected, because of a large number of asymptomatic cases. We provide an efficient, easy to compute and robust lower bound estimator for the number of undetected cases. METHODS: A modified version of the Chao estimator is proposed, based on the cumulative time-series distributions of cases and deaths. Heterogeneity has been addressed by assuming a geometrical distribution underlying the data generation process. An (approximated) analytical variance of the estimator has been derived to compute reliable confidence intervals at 95% level. RESULTS: A motivating application to the Austrian situation is provided and compared with an independent and representative study on prevalence of Covid-19 infection. Our estimates match well with the results from the independent prevalence study, but the capture-recapture estimate has less uncertainty involved as it is based on a larger sample size. Results from other European countries are mentioned in the discussion. The estimated ratio of the total estimated cases to the observed cases is around the value of 2.3 for all the analyzed countries. CONCLUSIONS: The proposed method answers to a fundamental open question: "How many undetected cases are going around?". CR methods provide a straightforward solution to shed light on undetected cases, incorporating heterogeneity that may arise in the probability of being detected.

Extent of Mucosal Inflammation in Ulcerative Colitis Influences the Clinical Remission Induced by Vedolizumab.

Randomized controlled clinical trials and real-life observations indicate that less than 50% of patients with Crohn's disease (CD) or ulcerative colitis (UC) respond to vedolizumab, a humanized monoclonal antibody that blocks the α4ß7 integrin. Since α4ß7-expressing lymphocytes mainly infiltrate the left colon, we assessed whether localization of CD and UC influences vedolizumab-induced remission. One hundred and eighty-one patients (74 CD and 107 UC) receiving vedolizumab in 3 referral centers were retrospectively evaluated for clinical remission at week 14. Demographic and clinical characteristics were compared between remitters and non-responders, and multivariable multinomial analysis was performed to identify predictors of remission. Remission was achieved in 17 CD (23%) and 34 UC (32%) patients, respectively. In CD, localization of the lesions did not influence clinical remission. In UC, the remitters had more frequently a distal/left-sided colitis (21/34, 62%) as compared to the non-responders (9/47, 19%), and extensive colitis was more frequent in the non-responders (38/47, 81%) than in the remitters (13/34, 38%). The multivariable multinomial analysis showed that distal/left-sided colitis was associated with a higher probability of clinical remission while extensive colitis was inversely associated with induction of remission. Data indicate that UC patients with distal or left-sided colitis are more likely to achieve remission than patients with extensive colitis following vedolizumab treatment.

Respiratory Tract Infections in Inflammatory Bowel Disease Patients Taking Vedolizumab: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The ongoing COVID-19 pandemic has raised concerns about the risk of SARS-CoV-2 infection in patients with Crohn's disease (CD) and patients with ulcerative colitis (UC) taking immunosuppressants or biologics. We conducted a systematic review and meta-analysis to assess the risk of respiratory infections in patients with inflammatory bowel disease (IBD) treated with vedolizumab. We searched PubMed, EMBASE and Scopus to identify randomized controlled trials (RCT) comparing vedolizumab to placebo in patients with IBD. Outcomes were the rate of respiratory tract infections (RTI), upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI) among patients receiving vedolizumab as compared with placebo. Pooled rates were reported as Odds Ratios (OR) with 95% Confidence Interval (CI). Eight RCT involving 3,287 patients (1873 CD and 1415 UC) were analyzed; 2,493 patients received vedolizumab and 794 received placebo. The rates of RTI and URTI were statistically higher in vedolizumab-treated patients compared to placebo [OR = 1.63; 95% CI (1.07-2.49); OR = 1.64 95% CI (1.07-2.53) respectively]. UC patients, but not CD patients, receiving vedolizumab had a higher risk to develop RTI and URTI [OR = 1.98; 95% CI (1.41-2.77); OR = 2.02; 95% CI (1.42-2.87)] compared to placebo-treated patients. The number of LRTI was small in both treatment groups. Data confirm the good safety profile of vedolizumab even though RTI were more frequent in patients receiving vedolizumab and the risk of URTIs was significantly higher in patients with UC.

A flexible ratio regression approach for zero-truncated capture-recapture counts.

Capture-recapture methods are used to estimate the size of a population of interest which is only partially observed. In such studies, each member of the population carries a count of the number of times it has been identified during the observational period. In real-life applications, only positive counts are recorded, and we get a truncated at zero-observed distribution. We need to use the truncated count distribution to estimate the number of unobserved units. We consider ratios of neighboring count probabilities, estimated by ratios of observed frequencies, regardless of whether we have a zero-truncated or an untruncated distribution. Rocchetti et al. (2011) have shown that, for densities in the Katz family, these ratios can be modeled by a regression approach, and Rocchetti et al. (2014) have specialized the approach to the beta-binomial distribution. Once the regression model has been estimated, the unobserved frequency of zero counts can be simply derived. The guiding principle is that it is often easier to find an appropriate regression model than a proper model for the count distribution. However, a full analysis of the connection between the regression model and the associated count distribution has been missing. In this manuscript, we fill the gap and show that the regression model approach leads, under general conditions, to a valid count distribution; we also consider a wider class of regression models, based on fractional polynomials. The proposed approach is illustrated by analyzing various empirical applications, and by means of a simulation study.

Modeling delay to diagnosis for amyotrophic lateral sclerosis: under reporting and incidence estimates.

BACKGROUND: This paper provides a strategy to obtain a reliable estimate of the incidence rate for Amyotrophic lateral sclerosis based on data from the National Registry of Rare Diseases (NRRD). In fact, unobserved cases may be due to the fact that "a long time" may intercour between the suspect of having the disease (onset) and the date the disease is diagnosed. Potential factors that may influence the probability of experiencing the event (diagnosis) conditionally on the onset (suspected) are investigated. Since we are treating rare diseases, the role of social and economic factors is not that obvious; latent as well as observed factors may influence the delay to diagnosis. METHODS: We use a semiparametric estimator based on the distribution of delay to diagnosis to account for potential underreporting. In particular, we propose to adopt an Horvitz-Thompson based estimator to correct the incidence figure that can be derived for the period 2007-2009 from the NRRD, Italy. RESULTS: The incidence estimates obtained by adopting the proposed approach are about 1 case per 100000 inhabitants and despite they let recovering a good part of underreporting, they are still far from ALS incidence international ranges between 1.5 and 2.5. However, by looking only at northern Italy, the incidence estimates we can derive are coherent with those known internationally. CONCLUSIONS: These results confirm the existence of substantial differences in reporting accuracy, and point out where the system of data collection must be improved. In particular, when reliable individual characteristics will be available, they could be employed to refine the proposed estimator.