Maackia amurensis seed lectin (MASL) and soluble human podoplanin (shPDPN) sequence analysis and effects on human oral squamous cell carcinoma (OSCC) cell migration and viability.

Maackia amurensis lectins serve as research and botanical agents that bind to sialic residues on proteins. For example, M. amurensis seed lectin (MASL) targets the sialic acid modified podoplanin (PDPN) receptor to suppress arthritic chondrocyte inflammation, and inhibit tumor cell growth and motility. However, M. amurensis lectin nomenclature and composition are not clearly defined. Here, we sought to definitively characterize MASL and its effects on tumor cell behavior. We utilized SDS-PAGE and LC-MS/MS to find that M. amurensis lectins can be divided into two groups. MASL is a member of one group which is composed of subunits that form dimers, evidently mediated by a cysteine residue in the carboxy region of the protein. In contrast to MASL, members of the other group do not dimerize under nonreducing conditions. These data also indicate that MASL is composed of 4 isoforms with an identical amino acid sequence, but unique glycosylation sites. We also produced a novel recombinant soluble human PDPN receptor (shPDPN) with 17 threonine residues glycosylated with sialic acid moieties with potential to act as a ligand trap that inhibits OSCC cell growth and motility. In addition, we report here that MASL targets PDPN with very strong binding kinetics in the nanomolar range. Moreover, we confirm that MASL can inhibit the growth and motility of human oral squamous cell carcinoma (OSCC) cells that express the PDPN receptor. Taken together, these data characterize M. amurensis lectins into two major groups based on their intrinsic properties, clarify the composition of MASL and its subunit isoform sequence and glycosylation sites, define sialic acid modifications on the PDPN receptor and its ability to act as a ligand trap, quantitate MASL binding to PDPN with KD in the nanomolar range, and verify the ability of MASL to serve as a potential anticancer agent.

Assessment of antidepressant-like effects of dextromethorphan on differential reinforcement of low-rate 72-s performance in rats.

The effectiveness of ketamine for treatment-resistant depression along with several other clinical advantages, such as rapid onset and reduced adverse effects associated with serotonin transporter inhibition, has garnered interest in other similar acting psychedelics as novel antidepressant drugs. The antitussive dextromethorphan exhibits glutamate N-methyl-d-aspartate receptor antagonism, sigma-1 receptor agonism, and serotonin reuptake inhibition, which has exhibited antidepressant effects in limited human studies and animal models. The present study sought to further examine dextromethorphan using a differential reinforcement of low-rate 72-s schedule, which can be used to screen antidepressant drugs, in male and female rats. The tricyclic antidepressant drug imipramine and the psychostimulant d-amphetamine also were examined. Sex differences were not shown for baseline performance or for the drugs tested. Further, performance did not differ between the estrus and diestrus stages. Dextromethorphan alone and with quinidine produced an antidepressant-like effect by reducing the number of responses emitted, increasing the number of reinforcers earned, and shifting inter-response times to the right, although significant response suppression occurred at these doses. An antidepressant-like effect was shown with imipramine, but d-amphetamine increased the number of responses emitted and did not affect the number of reinforcers earned. The present findings provide additional support for antidepressant effects produced by dextromethorphan.

Hospital-acquired influenza infections detected by a surveillance system over six seasons, from 2010/2011 to 2015/2016.

BACKGROUND: In addition to outbreaks of nosocomial influenza, sporadic nosocomial influenza infections also occur but are generally not reported in the literature. This study aimed to determine the epidemiologic characteristics of cases of nosocomial influenza compared with the remaining severe cases of severe influenza in acute hospitals in Catalonia (Spain) which were identified by surveillance. METHODS: An observational case-case epidemiological study was carried out in patients aged ≥18 years from Catalan 12 hospitals between 2010 and 2016. For each laboratory-confirmed influenza case (nosocomial or not) we collected demographic, virological and clinical characteristics. We defined patients with nosocomial influenza as those admitted to a hospital for a reason other than acute respiratory infection in whom ILI symptoms developed ≥48 h after admission and influenza virus infection was confirmed using RT-PCR. Mixed-effects regression was used to estimate the crude and adjusted OR. RESULTS: One thousand seven hundred twenty-two hospitalized patients with severe laboratory-confirmed influenza virus infection were included: 96 (5.6%) were classified as nosocomial influenza and more frequently had > 14 days of hospital stay (42.7% vs. 27.7%, P < .001) and higher mortality (18.8% vs. 12.6%, P < .02). The variables associated with nosocomial influenza cases in acute-care hospital settings were chronic renal disease (aOR 2.44 95% CI 1.44-4.15) and immunodeficiency (aOR 1.79 95% CI 1.04-3.06). CONCLUSIONS: Nosocomial infections are a recurring problem associated with high rates of chronic diseases and death. These findings underline the need for adherence to infection control guidelines.

Emotional Reactivity as a Vulnerability for Psychogenic Nonepileptic Seizures? Responses While Reliving Specific Emotions.

OBJECTIVE: Dysfunction in emotional processes is a hypothesized contributor to functional neurological disorders (FNDs), yet few studies have evoked real-time emotion during multimethod assessment incorporating subjective, behavioral, and psychophysiological indicators. This approach may reveal clinical and neurobiological vulnerability to FND and clarify how dysfunctional emotional processes serve as perpetuating factors. METHODS: Eleven participants with video-EEG-confirmed diagnoses of psychogenic nonepileptic seizures (PNES) were compared with 49 seizure-free trauma control subjects (TCs) with or without clinically elevated posttraumatic stress symptoms (25 clinically elevated [TC-clin], 24 not clinically elevated [TC-nonclin]). Participants recalled and described memories evoking anger, shame, happiness, and neutral feelings. RESULTS: Even though PNES patients and TCs reported similar amounts of emotional experience, PNES patients reported more difficulty reliving emotions and were less likely to complete the relived shame task. During and after reliving happiness, PNES and TC-clin groups showed respiratory sinus arrhythmia (RSA) decreases, indicating parasympathetic withdrawal, whereas the TC-nonclin group showed RSA increases. CONCLUSIONS: Findings from this pilot study are consistent with previous research and clinical observations that emotional engagement may be more effortful for PNES patients. Patterns of RSA change, which may also point to greater effortful engagement, were similar in PNES and TC-clin groups, suggesting that traumatic stress reactions may play a part. At the same time, experience of greater difficulty or avoidance may be even greater among PNES patients. Especially when regulatory resources are already limited, accumulated effort, coupled with self-threatening contexts such as shame, may be particularly problematic for those with PNES and perhaps other FNDs.

Effectiveness of antiviral treatment in preventing death in severe hospitalised influenza cases over six seasons.

We investigated the predictors of neuraminidase inhibitor (NAI) treatment in severe hospitalised influenza cases and the association between antiviral treatment and mortality. An observational epidemiological study was carried out in Catalonia (Spain) during 2010-2016 in patients aged ⩾18 years. Severe hospitalised cases of laboratory-confirmed influenza requiring hospitalisation were included. We collected demographic, virological and clinical characteristics. Mixed-effects logistic regression was used to estimate crude and adjusted odds ratio (aOR). We included 1727 hospitalised patients, of whom 1577 (91.3%) received NAI. Receiving NAI ⩽48 h after onset of clinical symptoms (aOR 0.37, 95% confidence interval (CI) 0.22-0.63), ⩽3 days (aOR 0.49, 95% CI 0.30-0.79) and ⩽5 days (aOR 0.50, 95% CI 0.32-0.79) was associated with a reduction in deaths. In patients admitted to the intensive care unit (ICU) (595; 34.5%), treatment ⩽48 h (aOR 0.32, 95% CI 0.14-0.74), ⩽3 days (aOR 0.44, 95% CI 0.20-0.97) and ⩽5 days (aOR 0.45, 95% CI 0.22-0.96) was associated with a reduction in deaths. Receiving treatment >5 days after onset of clinical symptoms was not associated with the reduction in deaths in hospitalised patients or those admitted to the ICU. NAI treatment of hospitalised patients with severe confirmed influenza was effective in avoiding death, mainly when administered ⩽48 h after symptom onset, but also when no more than 5 days had elapsed.

Diagnostic utility of the Minnesota Multiphasic Personality Inventory-2 Restructured Form in the epilepsy monitoring unit: Considering sex differences.

Psychological assessment measures are frequently used to evaluate patients in epilepsy monitoring units. One goal of that assessment is to contribute information that may help with differential diagnosis between epilepsy and psychogenic nonepileptic seizures (PNES). The Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF) is one such measure. Del Bene et al. (2017) recently published an analysis that was the first to compare MMPI-2-RF scale elevations between diagnostic groups stratified by sex. The purpose of the present study was to replicate that analysis in a larger sample. Similar to previous work, we found that both men and women with PNES were more likely than men and women with epilepsy to report high levels of somatic complaints (2 to 5 times greater odds of somatic symptom reporting) and a variety of types of complaints. Mood disturbance scales were not significantly elevated in our PNES sample. Results contribute to the small body of research on sex differences in patients with PNES and suggest that somatization is a key characterization across sexes.

Value of innovation in hematologic malignancies: a systematic review of published cost-effectiveness analyses.

We analyzed cost-effectiveness studies related to hematologic malignancies from the Tufts Medical Center Cost-Effectiveness Analysis Registry (www.cearegistry.org), focusing on studies of innovative therapies. Studies that met inclusion criteria were categorized by 4 cancer types (chronic myeloid leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and multiple myeloma) and 9 treatment agents (interferon-α, alemtuzumab, bendamustine, bortezomib, dasatinib, imatinib, lenalidomide, rituximab alone or in combination, and thalidomide). We examined study characteristics and stratified cost-effectiveness ratios by type of cancer, treatment, funder, and year of study publication. Twenty-nine studies published in the years 1996-2012 (including 44 cost-effectiveness ratios) met inclusion criteria, 22 (76%) of which were industry funded. Most ratios fell below $50,000 per quality-adjusted life-years (QALY) (73%) and $100,000/QALY (86%). Industry-funded studies (n = 22) reported a lower median ratio ($26,000/QALY) than others (n = 7; $33,000/QALY), although the difference was not statistically significant. Published data suggest that innovative treatments for hematologic malignancies may provide reasonable value for money.

EXAMINING EVIDENCE IN U.S. PAYER COVERAGE POLICIES FOR MULTI-GENE PANELS AND SEQUENCING TESTS.

OBJECTIVES: The aim of this study was to examine the evidence payers cited in their coverage policies for multi-gene panels and sequencing tests (panels), and to compare these findings with the evidence payers cited in their coverage policies for other types of medical interventions. METHODS: We used the University of California at San Francisco TRANSPERS Payer Coverage Registry to identify coverage policies for panels issued by five of the largest US private payers. We reviewed each policy and categorized the evidence cited within as: clinical studies, systematic reviews, technology assessments, cost-effectiveness analyses (CEAs), budget impact studies, and clinical guidelines. We compared the evidence cited in these coverage policies for panels with the evidence cited in policies for other intervention types (pharmaceuticals, medical devices, diagnostic tests and imaging, and surgical interventions) as reported in a previous study. RESULTS: Fifty-five coverage policies for panels were included. On average, payers cited clinical guidelines in 84 percent of their coverage policies (range, 73-100 percent), clinical studies in 69 percent (50-87 percent), technology assessments 47 percent (33-86 percent), systematic reviews or meta-analyses 31 percent (7-71 percent), and CEAs 5 percent (0-7 percent). No payers cited budget impact studies in their policies. Payers less often cited clinical studies, systematic reviews, technology assessments, and CEAs in their coverage policies for panels than in their policies for other intervention types. Payers cited clinical guidelines in a comparable proportion of policies for panels and other technology types. CONCLUSIONS: Payers in our sample less often cited clinical studies and other evidence types in their coverage policies for panels than they did in their coverage policies for other types of medical interventions.

When Does FDAMA Section 114 Apply? Ten Case Studies.

BACKGROUND: Section 114 of the Food and Drug Administration Modernization Act of 1997 regulates the promotion of health economic information by pharmaceutical companies to US health plans. Greater clarity is important given demands by payers and other stakeholders for evidence of value. OBJECTIVES: To develop hypothetical case studies of health economic promotions to examine legal and policy implications. METHODS: We constructed for pedagogical purposes 10 categories of potential health economic promotions. We generated hypothetical case studies for each category, including questions about whether each might be allowable under Section 114. The case studies were developed around the following categories: 1) costing out on-label clinical end points; 2) promotion of a costing exercise to physicians working in an accountable care organization setting; 3) burden-of-illness claims; 4) economic analysis of a formulary restriction policy; 5) extrapolations to doses, populations, or settings not covered in trials; 6) adherence claims; 7) "utilization of care" as a secondary end point in randomized clinical trials; 8) costing out a competitor drug's adverse event; 9) economic analysis of comparative effectiveness claims using an indirect treatment comparison; and 10) extrapolating from surrogate to long-term outcomes in an economic model. DISCUSSION: Most cases seem to fall into a gray zone given haziness around what constitutes "competent and reliable evidence" and "directly relate[d]" to an approved indication. In practice, it is difficult to know what the section allows given the imprecision of the statute and lack of guidance about its scope. CONCLUSION: Ideally, future guidance will provide clarity and flexibility.

The changing face of the cost-utility literature, 1990-2012.

OBJECTIVES: Cost-utility analyses (CUAs) have been published widely over the years to measure the value of health care interventions. We investigated the growth and characteristics of CUAs in the peer-reviewed English-language literature through 2012. METHODS: We analyzed data from the Tufts Medical Center Cost-Effectiveness Analysis (CEA) Registry, a database containing more than 3700 English-language CUAs published through 2012. We summarized various study characteristics (e.g., intervention type, funding source, and journal of publication) and methodological practices (e.g., use of probabilistic sensitivity analysis) over three time periods: 1990 to 1999, 2000 to 2009, and 2010 to 2012. We also examined CUAs by country, region, and the degree to which diseases studied correlate with disease burden. RESULTS: The number of published CUAs rose from 34 per year from 1990 to 1999 to 431 per year from 2010 to 2012. The proportion of studies focused on the United States declined from 61% during 1990 to 1999 to 35% during 2010 to 2012 (P < 0.0001). Although still small compared with CUAs in higher income countries, the number of CUAs focused on lower and middle-income countries has risen sharply. A large fraction of studies pertain to pharmaceuticals (46% during 2010-2012). In recent years, most studies included probabilistic sensitivity analysis (67% during 2010-2012). Journals publishing CUAs vary widely in the percentage of their studies funded by drug companies. Some conditions, such as injuries, have high burden but few CUAs. CONCLUSIONS: Our review reveals considerable growth and some change in the cost-utility literature in recent years. The data suggest growing interest in cost-utility methodology, particularly in non-Western countries.

Lymphogranuloma venereum in Barcelona, 2007-2012: the role of seroadaptation in men who have sex with men.

This study describes the incidence rate of reported lymphogranuloma venereum (LGV) in men who have sex with men (MSM) in Barcelona from 2007 to 2012. Epidemiological, clinical and sexual behaviour characteristics of LGV cases are described. Seroadaptive behaviours as a transmission risk factor were assessed by a telephone questionnaire during 2012. Data were handled on a strictly confidential basis. LGV annual rate ratios in MSM were compared with cases from 2007. Differences were statistically analysed with a Poisson test. The incidence rate of LGV in MSM aged 15-69 years ranged from 32·1/105 MSM per year in 2007 to 182·7/105 MSM per year in 2012. In 2012, 31/51 LGV cases (61%) answered the telephone questionnaire, of which 84% (26/31) were HIV positive, 39% (12/31) reported having sex according to their partners' serostatus and 7% (2/31) used strategic positioning. The incidence of LGV has increased since 2007 and mainly affects HIV-positive MSM. It is probable that seroadaptation has facilitated LGV transmission.

Influence of leaching solution and catchment location on the fluorescence of water-soluble organic matter.

Organic matter (OM) plays a significant role in biogeochemical processes in soil and water systems. Water-soluble organic matter (WSOM) leached from soil samples is often analyzed as representative of potentially mobile OM. However, there are many WSOM extraction methods in the literature with no clear guidelines for method selection. In this study, four common leaching solutions (0.5 M K2SO4, 0.01 M CaCl2, 2 M KCl, and H2O) were used to extract WSOM from various locations within a forested catchment. Fluorescence spectroscopy was used to analyze the impact of extraction method on WSOM chemistry. While all four methods consistently identified chemical differences between WSOM from a north-facing slope, south-facing slope, and riparian zone, there were clear differences in fluorescence signals between the leaching methods. All three salt solutions contained WSOM with a higher fluorescence index and humification index than WSOM leached with H2O, suggesting the presence of salts releases different fractions of the soil organic matter. A parallel factor analysis (PARAFAC) model developed from the leachates identified a distinctive soil humic fluorophore observed in all samples and fluorescent artifacts present in H2O-leached samples.

Epidemiology of tuberculosis in big cities of the European Union and European Economic Area countries.

This cross-sectional survey aimed to examine the epidemiology of tuberculosis (TB) in European Union (EU) and European Economic Area (EEA) cities with populations greater than 500,000. National TB programme managers were asked to provide data on big city population size, total number of notified TB cases in big cities and national notification rate for 2009. A rate ratio was calculated using the big city TB notification rate as a numerator and country TB notification rate, excluding big city TB cases and population, as a denominator. Twenty of the 30 EU/EEA countries had at least one big city. Pooled rate ratios were 2.5, 1.0, and 0.7 in low-, intermediate- and high-incidence countries respectively. In 15 big cities, all in low-incidence countries, rate ratios were twice the national notification rate. These data illustrate the TB epidemiology transition, a situation whereby TB disease concentrates in big cities as national incidence falls, most likely as a result of the higher concentration of risk groups found there. This situation requires targeted interventions and we recommend that big city TB data, including information about patients' risk factors, are collected and analysed systematically, and that successful interventions are shared.

Tuberculosis control in big cities and urban risk groups in the European Union: a consensus statement.

In low-incidence countries in the European Union (EU), tuberculosis (TB) is concentrated in big cities, especially among certain urban high-risk groups including immigrants from TB high-incidence countries, homeless people, and those with a history of drug and alcohol misuse. Elimination of TB in European big cities requires control measures focused on multiple layers of the urban population. The particular complexities of major EU metropolises, for example high population density and social structure, create specific opportunities for transmission, but also enable targeted TB control interventions, not efficient in the general population, to be effective or cost effective. Lessons can be learnt from across the EU and this consensus statement on TB control in big cities and urban risk groups was prepared by a working group representing various EU big cities, brought together on the initiative of the European Centre for Disease Prevention and Control. The consensus statement describes general and specific social, educational, operational, organisational, legal and monitoring TB control interventions in EU big cities, as well as providing recommendations for big city TB control, based upon a conceptual TB transmission and control model.

Epidemiological evolution and economic impact of the COVID-19 pandemic in the European Union and worldwide and effects of control strategies on them: An ecological study.

OBJECTIVE: To evaluate the epidemiological evolution and economic impact of COVID-19 pandemic in the European Union (EU) and worldwide, and the effects of control strategies on them. MATERIAL AND METHODS: We collected incidence, mortality, and gross domestic product (GDP) data between the first quarter of 2020 and of 2023. Then, we reviewed the effectiveness of the mitigation and zero-COVID control strategies. The statistical analysis was done calculating the incidence rate ratio (IRR) of two rates and its 95% confidence interval (CI). RESULTS: In the EU, COVID-19 presented six epidemic waves. The sixth one at the beginning of 2022 was the biggest. Globally, the biggest wave occurred at the beginning of 2023. Highest mortality rates were observed in the EU during 2020-2021 and globally at the beginning of 2021. In mitigation countries, mortality was much higher than in zero-COVID countries (IRR=6.82 [95% CI: 6.14-7.60]; p<0.001). A GDP reduction was observed worldwide, except in Asia. None of the eight zero-COVID countries presented a GDP growth percentage lower than the EU percentage in 2020, and 3/8 in 2022 (p=0.054). COVID-19 pandemic caused epidemic waves with high mortality rates and a negative impact on GDP. CONCLUSION: The zero-COVID strategy was more effective in avoiding mortality and potentially had a lower impact on GDP in the first pandemic year.

Effects of cadherin mediated contact normalization on oncogenic Src kinase mediated gene expression and protein phosphorylation.

Nontransformed cells form heterotypic cadherin junctions with adjacent transformed cells to inhibit tumor cell growth and motility. Transformed cells must override this form of growth control, called "contact normalization", to invade and metastasize during cancer progression. Heterocellular cadherin junctions between transformed and nontransformed cells are needed for this process. However, specific mechanisms downstream of cadherin signaling have not been clearly elucidated. Here, we utilized a ß-catenin reporter construct to determine if contact normalization affects Wnt signaling in transformed cells. ß-catenin driven GFP expression in Src transformed mouse embryonic cells was decreased when cultured with cadherin competent nontransformed cells compared to transformed cells cultured with themselves, but not when cultured with cadherin deficient nontransformed cells. We also utilized a layered culture system to investigate the effects of oncogenic transformation and contact normalization on gene expression and oncogenic Src kinase mediated phosphorylation events. RNA-Seq analysis found that cadherin dependent contact normalization inhibited the expression of 22 transcripts that were induced by Src transformation, and increased the expression of 78 transcripts that were suppressed by Src transformation. Phosphoproteomic analysis of cells expressing a temperature sensitive Src kinase construct found that contact normalization decreased phosphorylation of 10 proteins on tyrosine residues that were phosphorylated within 1 h of Src kinase activation in transformed cells. Taken together, these results indicate that cadherin dependent contact normalization inhibits Wnt signaling to regulate oncogenic kinase activity and gene expression, particularly PDPN expression, in transformed cells in order to control tumor progression.

Hepatitis C virus reinfection among prisoners with sustained virological response after treatment for chronic hepatitis C.

BACKGROUND & AIMS: We estimated HCV reinfection rate and its associated risk factors in inmates with chronic hepatitis C who had achieved sustained virological response (SVR) after completing combination therapy while in prison. METHODS: Individuals who had achieved an SVR after treatment provided from January 2003 to December 2009 at four prisons in Catalonia, had been tested annually for HCV RNA and were in prison during 2010, were invited to complete a questionnaire regarding risk factors for reinfection. Incidence rate was calculated as 100 person-years of follow-up. Risk factors potentially associated with reinfection were evaluated by bivariate log-rank test and multivariate Cox regression analysis. RESULTS: One hundred and nineteen subjects who had achieved an SVR agreed to participate. 98% were male, with a median age of 33.3 ± 6.3 years and 81% had a history of injection drug use (IDU). After a mean follow-up of 1.4 years, HCV reinfection was identified in nine former IDUs, seven with HCV genotype switch, for an overall reinfection rate of 5.27 cases per 100 person-years. Reinfection incidence was significantly higher among active drug users (HR=12.47; 95% CI: 2.90-53.71), HIV co-infected (HR=9.95; 95% CI: 1.73-57.34), and those engaging in more than one risk behaviors after treatment (HR=7.47; 95% CI: 1.19-46.89). CONCLUSIONS: HCV reinfection among inmates after successful treatment is high especially in those with ongoing IDU. Preventative interventions at diagnosis and during and after HCV treatment should be strongly reinforced.

Two simultaneous botulism outbreaks in Barcelona: Clostridium baratii and Clostridium botulinum.

Botulism is a severe neuroparalytic disorder that can be potentially life-threatening. In Barcelona, Spain, no outbreaks had been reported in the past 25 years. However, in September 2011, two outbreaks occurred involving two different families. A rare case of Clostridium baratii which produced a neurotoxin F outbreak was detected in five family members who had shared lunch, and several days before that another family was affected by C. botulinum toxin A which was probably present in homemade pâté.

Increase in gonorrhoea among very young adolescents, Catalonia, Spain, January 2012 to June 2013.

Between January 2012 and June 2013, 27 sexually transmitted infections were reported in adolescents aged 13-15 years in Catalonia, Spain. In the first half of 2013, there were nine cases of gonorrhoea, while in the same period of 2012, there was one. In June 2013, two gonorrhoea cases aged 13-14 years, linked to a common source through a social network, were reported. The public health response should be adapted to this vulnerable population.

Decline of tuberculosis notification rate in different populations and regions in Portugal, 2010-2017.

BACKGROUND: Tuberculosis (TB) incidence declined in Portugal in recent decades, but trends differ between regions and population subgroups. We investigated these differences to inform prevention and control programmes. METHODS: We extracted TB notifications from the Portuguese National TB Surveillance System (SVIG-TB) in 2010-2017, disaggregated by region, age group, nationality and HIV status. We calculated notification rates using denominators from the Portuguese National Institute of Statistics and the Joint United Nations Programme on HIV/AIDS and performed stratified time series analysis. We estimated interannual decline percentages and 95% confidence intervals (CI) using Poisson and binomial negative regression models. RESULTS: The overall TB notification rate decreased from 25.7 to 17.5/100,000 population from 2010 to 2017 (5.2%/year) in Portugal. Interannual decline did not differ significantly between regions, but it was smaller amongst non-Portuguese nationals (-1.57% [CI: -4.79%, 1.75%] vs -5.85% [CI: -6.98%, -4.70%] in Portuguese nationals); children under five years of age (+1.77% [CI: -4.61%, 8.58%] vs -5.38% [CI: -6.33%, -4.42%] in other age groups); and HIV-negative people (-6.47% [CI: -9.10%, -3.77%] vs -11.29% [CI; -17.51%, -4.60%] in HIV-positive). CONCLUSIONS: The decline in TB notification rates in Portugal during the study period has been steady. However, the decline amongst non-Portuguese nationals, children under five years of age and non-infected-HIV patients was lower. No significant differences were observed between regions. Changes in TB epidemiology in specific risk groups and geographical areas should be closely monitored to achieve the objectives of the End TB Strategy. We recommend intensifying screening of TB in the subpopulations identified.