Integrated Lymphopenia Analysis in Younger and Older Patients With Multiple Sclerosis Treated With Cladribine Tablets

Cladribine tablets (CladT) preferentially reduce B and T lymphocyte levels. As aging is associated with a decline in immune function, the effect of CladT on lymphocyte levels may differ by age. This post hoc analysis combined data from the Phase 3 CLARITY, CLARITY Extension, and ORACLE-MS studies to examine the effect of age (≤50 or >50 years) on lymphopenia following CladT 3.5 mg/kg (CladT3.5; cumulative dose over 2 years) treatment over 96 weeks. Both CladT3.5 and placebo were given over Weeks 1 and 5 (Year 1 treatment) and Weeks 48 and 52 (Year 2 treatment) from the start of the studies. Absolute lymphocyte count (ALC) and levels of lymphocyte subsets were examined in 1564 patients (Age ≤50 [placebo: N=566; CladT3.5: N=813]; Age >50 [placebo: N=75; CladT3.5: N=110]). In both age groups, following CladT3.5 treatment, nadir for ALC occurred at Week 9 (8 weeks following start of Year 1 treatment) and Week 55 (7 weeks following start of Year 2 treatment) of the 96-week period; for CD19+ B lymphocytes, nadir occurred at Week 9 (Year 1) and Week 52 (Year 2). For CD4+ T lymphocytes, nadir occurred at Week 16 (Year 1) in both age groups, and at Weeks 60 and 72 (Year 2) in the Age ≤50 and >50 groups, respectively. Nadir for CD8+ T lymphocytes occurred at Week 16 (Year 1) and Week 72 (Year 2) in the Age ≤50 group and levels remained in the normal range; nadir occurred at Week 9 (Year 1) and Week 96 (Year 2) in the Age >50 group. Lymphocyte recovery began soon after nadir following CladT3.5 treatment and median levels reached normal range by end of the treatment year in both age groups. By Week 96, ~25% of patients treated with CladT3.5 reported ≥1 episode of Grade ≥3 lymphopenia (Gr≥3L). The rate of certain infections was numerically higher in older versus younger patients who experienced Gr≥3L. In conclusion, CladT3.5 had a similar effect on ALC and lymphocyte subsets in both younger and older patient groups.

Download Full-text

Age-stratified pediatric reference values of lymphocytes in the Moroccan population

Human Antibodies ◽

10.3233/hab-200432 ◽

2020 ◽

pp. 1-10

Author(s):

Aicha El Allam ◽

Sara El Fakihi ◽

Hicham Tahoune ◽

Karima Sahmoudi ◽

Houria Bousserhane ◽

...

Keyword(s):

T Lymphocytes ◽

Reference Values ◽

Blood Lymphocyte ◽

Healthy Subjects ◽

Lymphocyte Subsets ◽

Age Groups ◽

Lymphocyte Subpopulation ◽

Study Group ◽

Moroccan Population ◽

Helper T Lymphocytes

The number of circulating lymphocytes is altered in a number of diseases including either increase (lymphocytosis) or decrease (lymphocytopenia). Therefore, the assessment of total blood lymphocyte numbers and the relative distribution of lymphocyte subsets is a critical front-line tool in the clinical diagnosis of a number of diseases, including pediatric diseases and disorders. However, the interpretation of this data requires comparison of patient’s results to reliable reference values. Blood lymphocyte subpopulation numbers are also subject to genetic polymorphisms, immunogenic and environmental factors and vary greatly between populations. While the best practice reference values should be established within local representative populations of healthy subjects, to date, Caucasian reference values are used in Morocco due to the absence of indigenous reference values. Potential differences in blood lymphocyte subpopulation reference values between Caucasian versus Moroccan populations can adversely affect the diagnosis of pediatric and childhood diseases and disorders such as primary immunodeficiency (PID) in Morocco. OBJECTIVE: The aim of this study was to establish the age-stratified normal reference values of blood lymphocyte subsets for the pediatric Moroccan population. METHODS: We measured the concentration of lymphocyte subpopulations by flow cytometry from 83 Moroccan healthy subjects stratified into 5 age groups of 0–1, 1–2, 2–6, 6–12 and > 12–18 (adult). RESULTS: The absolute and relative amounts of the main lymphocyte subsets of T-cells, B cells and Natural Killer (NK) cells were measured and compared to previously described reference values from Cameroonian, Turkish, American and Dutch populations. Additionally, we also observed an age-related decline in the absolute population sizes of lymphocyte subsets within our study group. Relative proportions of CD3+CD4+ helper T lymphocytes decreased with increasing age and by 12 years-adult age, both proportions of CD3+CD4+ helper T lymphocytes and CD3+CD8+ cytotoxic T lymphocytes, as well as CD3-CD19+ B lymphocytes were also decreased. Finally, we compared the median values and range of our Moroccan study group with that of published results from Cameroon, Turkey, USA and Netherlands and observed significant differences in median and mean values of absolute number and relative proportions of lymphocyte subsets especially at 0–1 years and 1–2 years age groups. Above age 12 years, the Moroccan values were lower. For NK cells, the Moroccan values are also lower. CONCLUSIONS: The results of this study have a significant impact in improving the threshold values of the references intervals routinely used in the diagnosis of paediatric diseases such as PIDs or mother-to-child transmitted HIV within the Moroccan population.

Download Full-text

Efficacy and safety of paclitaxel and carboplatin with bevacizumab for the first-line treatment of patients with nonsquamous non-small cell lung cancer (NSCLC): Analyses based on age in the phase III PointBreak and E4599 trials.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.8073 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 8073-8073 ◽

Cited By ~ 3

Author(s):

Corey J. Langer ◽

Mark A. Socinski ◽

Jyoti D. Patel ◽

Alan Sandler ◽

Joan H. Schiller ◽

...

Keyword(s):

Survival Benefit ◽

Age Groups ◽

Progression Free Survival ◽

Phase Iii ◽

Efficacy And Safety ◽

Hazard Ratios ◽

Level Data ◽

Significant Survival ◽

Grade 3 ◽

Post Hoc

8073 Background: A post hoc analysis of NSCLC (pts) ≥70 y in the pivotal E4599 trial found increased adverse events (AEs) and numerically decreased survival benefit associated with bevacizumab (BEV) vs pts <70 y. We evaluated the efficacy and safety of BEV by age in pts in a pooled dataset from the E4599 and PointBreak (PB) trials. Methods: Pts randomized to the PC (paclitaxel and carboplatin ) + BEV arms of E4599 and PB received P 200 mg/m2, C AUC 6, and BEV 15 mg/kg q3w for 6 (E4599) or 4 (PB) cycles; 1 pt in PB received 6 cycles. Eligible pts received maintenance BEV q3w until disease progression or unacceptable toxicity. Overall survival (OS), progression-free survival (PFS), and safety were assessed in pts grouped according to age (<65 y, 65–75 y, 70–75 y, <75 y, and ≥75 y). Pt-level data from the PC + BEV arms of E4599 and PB were pooled and compared with data from pts in the PC-alone arm of E4599. Results: PB and E4599 randomized 467 pts and 434 pts to PC + BEV, respectively. Baseline characteristics were balanced between age groups. OS and PFS hazard ratios (HRs) and increases in grade ≥3 AEs for the pooled pt cohort relative to E4599 PC-alone arm are shown (Table). Outcomes were similar in pts <70 y and ≥70 y, and data from the pooled population were similar to those seen in each individual trial (data not shown). Conclusions: In a pooled exploratory analysis of pt data from E4599 and PB, the statistically significant benefit associated with the addition of BEV to PC appeared consistent across all age groups <75y. Pts ≥75 y receiving BEV had a higher incidence of grade ≥3 AEs relative to PC alone with no statistically significant survival benefit, although an increase in grade ≥3 AEs was observed in all age groups. Clinical trial information: NCT00762034 and NCT00021060. [Table: see text]

Download Full-text

Epidemiologic and clinical characteristics of 3334 cases with pre-diagnosis coronavirus disease - 2019 (COVID-19) in Turkey

10.22541/au.161219182.26365222/v1 ◽

2021 ◽

Author(s):

Nur Simsek Yurt ◽

Metin Ocak ◽

Yusuf Can Yurt

Keyword(s):

Mortality Rate ◽

Clinical Features ◽

Age Groups ◽

Rt Pcr ◽

Laboratory Findings ◽

Reactive Protein ◽

Significant Difference ◽

Patient Groups ◽

Post Hoc

Introduction: As COVID-19 disease has rapidly spread across the world, its impact has grown with increasing number of cases and mortality rate in Turkey. Aim: The aim of this study is to examine epidemiologic and clinical features of the patients that admitted to the hospital with the pre-diagnosis of coronavirus disease-2019 (COVID-19) in Turkey. Method: In this retrospective study, epidemiologic and clinical features, laboratory findings, radiologic features, therapeutic approaches and survival conditions of the patients with the pre-diagnosis of COVID-19 from March 11th to June 30th, 2020. The all data of the cases were compared in 4 groups: 1st group for the confirmed cases reverse transcriptase polymerase chain reaction (RT-PCR) +, chest computed tomography (CT) +, 2nd group for the clinically diagnosed cases (RT-PCR- CT +), 3rd group for the mild and asymptomatic cases (RT-PCR + CT-), 4th group for the suspected cases (RT-PCR - CT -). Post-hoc analysis was performed to evaluate the differences among the groups. Results: In total, 3334 patients with the pre-diagnosis of COVID-19 admitted to the emergency department. Based on the post-hoc analyses, significant differences were found among the four groups in terms of their test results of leucocytes, hemoglobin, platelets, neutrophils, urea and C-reactive protein (CRP) (p<0.001). Furthermore, the factors of age groups, hospitalization, intensive care follow-up and mortality rate of the four groups showed a significant difference among the groups (p=0.001). Conclusion: Mean of leucocytes, neutrophile and platelet values of the patients with tested positive for the RT-PCR was found lower compared to the ones with tested negative for the RT-PCR. Mean of CRP values was found higher in patients with lung involvement compared to other patient groups.

Download Full-text

COVID-19 Epigenetics and Implications for Public Health

Coronaviruses ◽

10.2174/2666796701999201005212515 ◽

2020 ◽

Vol 01 ◽

Author(s):

Verda Tunalıgil ◽

Gülsen Meral ◽

Ahmet Katı ◽

Dhrubajyoti Chattopadhyay ◽

Amit Kumar Mandal

Keyword(s):

Chronic Conditions ◽

Empirical Investigation ◽

Age Groups ◽

Infectious Agent ◽

Well Being ◽

Epigenetic Mechanisms ◽

Age Group ◽

Epigenetic Changes ◽

Patient Groups ◽

Epigenetic Processes

Abstract:: Epigenetic changes in COVID-19 host, a pandemic-causing infectious agent that globally incapacitated communities in varying complexities and capacities are discussed, proposing an analogy that epigenetic processes contribute to disease severity and elevate the risk for death from infection. Percentages of hospitalization, with and without intensive care, in the presence of diseases with increased ACE2 expression, were compared, based on the best available data. Further analysis compared two different age groups, 19-64 and ≥65 years of age. The COVID-19 disease is observed to be the most severe in the 65-and-higher-age group with preexisting chronic conditions. This observational study is a non-experimental empirical investigation of the outcomes of COVID-19 in different patient groups. Results are promising for conducting clinical trials with intervention groups. To ultimately succeed in disease prevention, researchers and clinicians must integrate epigenetic mechanisms to generate valid prescriptions for global well-being.

Download Full-text

Flow cytometric analysis of T lymphocytes and cytokines in aqueous humor of patients with varicella zoster virus-mediated acute retinal necrosis

BMC Ophthalmology ◽

10.1186/s12886-021-01951-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hao Kang ◽

Yunbo Wei ◽

Ming Liu ◽

Di Yu ◽

Yong Tao

Keyword(s):

T Lymphocytes ◽

Varicella Zoster Virus ◽

Aqueous Humor ◽

T Lymphocyte ◽

Lymphocyte Subsets ◽

Flow Cytometric Analysis ◽

T Lymphocyte Subsets ◽

Varicella Zoster ◽

Flow Cytometric ◽

Cd8 T Lymphocytes

Abstract Background The purpose of this study is to investigate the aqueous humor (AH) T lymphocyte subsets and cytokines of acute retinal necrosis (ARN) to elucidate the immunologic inflammatory features of this disorder. Methods Three patients with ARN infected with varicella zoster virus (VZV) who underwent multiple intravitreal injections of ganciclovir were enrolled in this study. The control group consisted of four non-infectious patients with acute anterior uveitis (AAU). Flow cytometric analysis was performed on the lymphocyte subsets from the AH and peripheral blood (PB) samples during the active phase of intraocular inflammation. Five inflammatory cytokines were measured in each AH sample and various clinical characteristics were also assessed. Results VZV deoxyribonucleic acid (DNA) was detected by real-time polymerase chain reaction (PCR) in AH from all the ARN patients, who showed higher CD8+ T lymphocytes population in AH than the AAU patients (p = 0.006). CD4/CD8 ratios of T lymphocytes and the percentage of CD8 + CD25+ T lymphocytes in AH were significantly lower in ARN than in AAU (p = 0.006; p = 0.012). In the ARN patients, the percentages of CD4+ and CD8+ T lymphocytes in AH were higher than those found in PB. The percentage of CD4 + CD25+ T lymphocytes in AH was significantly higher than the proportion in PB in the AAU patients (p = 0.001). Immunoregulatory cytokine Interleukin-10 in AH was significantly elevated in the ARN patients in comparison with the case of the AAU patients (p = 0.036). In ARN, the copy number of VZV DNA in AH positively correlated with the percentage of CD8+ T lymphocytes in AH and negatively correlated with the CD4/CD8 ratio in AH during the course of disease treatment (p = 0.009, r = 0.92; p = 0.039, r = − 0.834). Conclusion The ARN patients caused by VZV had different intraocular T lymphocyte subsets and cytokines profile than those of the non-infectious patients. High percentages of CD8+ T lymphocytes and low CD4/CD8 T cell ratios may be a potential biomarker for diagnosis of viral-infectious uveitis. T lymphocytes examination at the inflammatory sites has the potential to become a useful research tool for differentiating viral and non-viral uveitis.

Download Full-text

Evaluation of Changes in Depression Levels of Bruxism Patients Treated With Botulinum Toxin-A

Journal of Advanced Oral Research ◽

10.1177/23202068211006554 ◽

2021 ◽

pp. 232020682110065

Author(s):

Deniz Erdil ◽

Nilsun Bagis ◽

Hakan Eren ◽

Melike Camgoz ◽

Kaan Orhan

Keyword(s):

Botulinum Toxin ◽

Botulinum Toxin A ◽

Age Groups ◽

Treatment Method ◽

Definitive Treatment ◽

Toxin A ◽

Physiological Factors ◽

Before And After ◽

The Mean ◽

Post Hoc

Aim: Bruxism is defined as the involuntary recurrent masticatory muscle activity characterized by gnashing, grinding, clenching of teeth, and/or pushing the mandible. Factors creating its etiology are peripheral (morphological) or central (physiopathological and physiological), and exogenous. Recently, among physiological factors, depression and bruxism were considered to be related. A definitive treatment method does not exist for bruxism; however, botulinum toxin-A (BT-A) application is an up-to-date and effective way of treatment. The present study is aimed to evaluate the levels of depression in bruxism patients treated with BT-A application. Materials and Methods: A total of 25 individuals (23 females and 2 males) who were diagnosed as bruxism patients were included in the study. 25 U of BT-A for each masseter muscle was injected into the patients. Patients were prospectively observed for a possible change in depression levels by using Beck’s Depression Inventory. The inventory was implemented before and six months after the BT-A application. Depression levels before and six months after the injection were compared. A paired t-test was used to compare “before” and “after” treatment values. One-way analysis of variance and post-hoc Tukey tests were used to evaluate the change in Beck’s Depression Inventory scores according to age groups. Results: The mean total score was 7.80 ± 8.10 before the treatment and 7.16 ± 6.52 six months after the treatment. The decrease in the mean score was not statistically significant ( P > .05). Conclusion: In conclusion, despite the decrease in the mean Beck’s Depression Inventory scores, a statistically significant decrease in the depression levels of patients was not observed.

Download Full-text

Birds of a Feather Flock Together: Disadvantageous Decision Making in Augmented Restless Legs Syndrome Patients with and without Impulse Control Disorders

Brain Sciences ◽

10.3390/brainsci11030383 ◽

2021 ◽

Vol 11 (3) ◽

pp. 383

Author(s):

Beatrice Heim ◽

Philipp Ellmerer ◽

Ambra Stefani ◽

Anna Heidbreder ◽

Elisabeth Brandauer ◽

...

Keyword(s):

Decision Making ◽

Restless Legs Syndrome ◽

Impulse Control ◽

Compulsive Sexual Behavior ◽

Structured Interviews ◽

Restless Legs ◽

Information Sampling ◽

Patient Groups ◽

Post Hoc ◽

Beads Task

Background: Augmentation (AUG) in patients with restless legs syndrome (RLS) can be associated with impulse control disorder (ICD) symptoms, such as compulsive sexual behavior, gambling disorder or compulsive shopping. In this study, we wanted to assess whether RLS patients with AUG differ in decision making from those patients who have augmentation and in addition ICD symptoms (AUG + ICD) in a post hoc analysis of a patient cohort assessed in a previous study. Methods: In total, 40 RLS patients with augmentation (19 AUG + ICD, 21 AUG without ICDs) were included. RLS diagnosis, severity, and diagnosis of augmentation were made by sleep disorder specialists. ICD symptoms were assessed using semi-structured interviews. All patients performed the beads task, which is an information sampling task where participants must decide from which of the two cups colored beads were drawn. Results were compared to 21 healthy controls (HC). Results: There was no difference in information sampling or irrational decision making between AUG and AUG + ICD patients (p = 0.67 and p = 1.00, respectively). Both patient groups drew less beads and made more irrational decisions than HC (all p-values < 0.03, respectively). Conclusions: Our results suggest that augmentation itself is associated with poorer decision making even in the absence of ICD symptoms. Further studies are necessary to explore whether rapid and hasty decision making are a harbinger of augmentation in RLS.

Download Full-text

Does body position, age, and heart rate induce IOP’s changes?

European Journal of Ophthalmology ◽

10.1177/11206721211023313 ◽

2021 ◽

pp. 112067212110233

Author(s):

Marcelina Sobczak ◽

Magdalena Asejczyk ◽

Malwina Geniusz

Keyword(s):

Heart Rate ◽

Body Position ◽

Age Groups ◽

Cardiovascular Parameters ◽

Entire Cohort ◽

Significant Difference ◽

Group A ◽

The Difference ◽

Group B ◽

Effect Of Age

Objectives: The main goal of this research was to determine the differences between the values of intraocular pressure (IOP) in the supine and sitting positions, and to assess the effect of age and cardiovascular parameters. Methods: Seventy-two healthy adults were enrolled and classified into age groups: 20–30 years (group A), 31–40 years (group B), and 41–71 years (group C). Corneal biometry and cardiovascular parameters, such as heart rate (HR), were measured. IOP measurements were taken in the sitting position (IOPS) and in the supine position (IOPL) using the iCare® Pro tonometer. Results: A significant difference between the IOPS and IOPL in the entire cohort was found ( p < 0.001). Regarding the age subgroups, a significant difference ( p < 0.001) between the IOPS and IOPL was obtained in group A (2.6 ± 1.6 mmHg) and group C (1.5 ± 1.3 mmHg). There were no significant differences in the IOPS between groups. The highest IOP values were obtained for group A. The correlations between HR and IOPS are statistically significant for group A and group B, and for HR and IOPL-S for group B only. Multivariate analysis showed that HR has a significant influence on the difference in IOP in the two body positions. Conclusion: A statistically significant difference between the effect of age and the values of IOPS and IOPL was shown. Cardiovascular parameters showed some relevant statistical dependencies, but with a rather marginal significance in young people. The influence of body position for the measurement of IOP for healthy subjects does not seem to matter, despite the fact that there are some dependencies that are statistically significant.

Download Full-text

An approach to assess stress in response to drive hunts using cortisol levels of wild boar (Sus scrofa)

Scientific Reports ◽

10.1038/s41598-021-95927-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Justine Güldenpfennig ◽

Marion Schmicke ◽

Martina Hoedemaker ◽

Ursula Siebert ◽

Oliver Keuling

Keyword(s):

Wild Boar ◽

Stress Hormones ◽

Age Groups ◽

Group Living ◽

Well Being ◽

Lower Saxony ◽

Cortisol Levels ◽

Negative Impacts ◽

The Impact ◽

Effect Of Age

AbstractHunting can easily be linked to stress in wildlife. Drive hunts performed two to three times in one area during the respective hunting period, are thought to decrease the pressure hunting places on wildlife. Nevertheless, the expression of cortisol—one of the main mammalian stress hormones—is considered to have negative impacts on animals’ well-being if expressed excessively, which may occur during some (especially repeated) hunting events. We explored the effect of drive hunts on cortisol levels in wild boar in Lower Saxony, Germany, compared these cortisol levels to reference values given by a similar study, and investigated the effect of age, sex, and pregnancy. Blood collected from wild boar shot on drive hunts was analysed using a radioimmunoassay. As expected, we observed elevated cortisol levels in all samples, however, we still found significant differences between age groups and sexes, as well as an influence of pregnancy on cortisol levels. The effect of drive hunts on cortisol levels appears to be weaker than predicted, while the effects of other variables, such as sex, are distinct. Only half of the evaluated samples showed explicitly increased cortisol levels and no significant differences were found between sampling months and locations. Group living animals and pregnant females showed significantly higher cortisol levels. The impact of hunting is measurable but is masked by natural effects such as pregnancy. Thus, we need more information on stress levels in game species.

Download Full-text

Efficacy and Safety of Teriflunomide in Multiple Sclerosis across Age Groups: Analysis from Pooled Pivotal and Real-world Studies

Journal of Central Nervous System Disease ◽

10.1177/11795735211028781 ◽

2021 ◽

Vol 13 ◽

pp. 117957352110287

Author(s):

Jiwon Oh ◽

Sandra Vukusic ◽

Klaus Tiel-Wilck ◽

Jihad Said Inshasi ◽

David Rog ◽

...

Keyword(s):

Multiple Sclerosis ◽

Real World ◽

Age Groups ◽

Phase Iii ◽

Efficacy And Safety ◽

Additional Group ◽

Disability Status ◽

Scale Scores ◽

Post Hoc ◽

Phase Ii And Iii

Background: Evidence suggests that efficacy and safety of disease-modifying treatments for multiple sclerosis may differ with age. We evaluate efficacy and safety of teriflunomide across age subgroups of patients from pooled clinical trials and real-world studies. Methods: Post hoc analyses of patients who received teriflunomide 14 mg in the pooled phase II and III TEMSO, TOWER, TENERE, and TOPIC core and extension studies (n = 1978), and the real-world Teri-PRO (n = 928) and TAURUS-MS I (n = 1126) studies were conducted. Data were stratified by age at study entry: ⩽25, >25 to ⩽35, >35 to ⩽45, and >45 years. In Teri-PRO and TAURUS-MS I, an additional group, >55 years, was assessed. Results: In the pooled core studies, teriflunomide reduced annualized relapse rate (ARR) versus placebo across all ages. Unadjusted ARRs remained low across age groups in pooled extensions (0.18-0.30), Teri-PRO (0.10-0.35), and TAURUS-MS I (0.14-0.35). Baseline Expanded Disability Status Scale scores were higher with age, but stable through core and extension studies (mean increases over 7 years: ⩽25 years, +0.59; >25 to ⩽35 years, +0.46; >35 to ⩽45 years, +0.35; >45 years, +0.81). Across age groups, adverse event (AE) incidences were 78.4% to 90.7% in pooled core and extension studies and Teri-PRO, and 29.2% to 37.7% in TAURUS-MS I; serious AE incidences were ⩽21.3% in all studies. In pooled phase III and Teri-PRO studies, lymphocyte count decreases over 1 year after initiating teriflunomide, and proportions of patients developing lymphopenia, were small across age groups. Conclusions: Teriflunomide efficacy was demonstrated regardless of age. Safety was generally consistent across age groups.

Download Full-text