scholarly journals Biological and Functional Changes in Healthy Adult Smokers Who Are Continuously Abstinent From Smoking for One Year: Protocol for a Prospective, Observational, Multicenter Cohort Study (Preprint)

2018 ◽  
Author(s):  
Cam Tuan Tran ◽  
Loyse Felber Medlin ◽  
Nicola Lama ◽  
Brindusa Taranu ◽  
Weeteck Ng ◽  
...  
Keyword(s):  
Cohort Study ◽  
Adverse Events ◽  
Clinical Chemistry ◽  
Risk Level ◽  
Functional Changes ◽  
Biomarkers Of Exposure ◽  
Quit Smoking ◽  
Study Results ◽  
Biomarkers Of Effect

BACKGROUND The harm of smoking results mainly from long-term exposure to harmful and potentially harmful constituents (HPHCs) generated by tobacco combustion. Smoking cessation (SC) engenders favorable changes of clinical signs, pathomechanisms, and metabolic processes that together could reduce the harm of smoking-related diseases to a relative risk level approximating that of never-smokers over time. In most SC studies, the main focus is on the quitting rate of the SC program being tested. As there is limited information in the literature on short to multiple long-term functional or biological changes following SC, more data on short to mid-term favorable impacts of SC are needed. OBJECTIVE The overall aim of the study was to assess the reversibility of the harm related to smoking over 1 year of continuous smoking abstinence (SA). This has been verified by assessing a set of biomarkers of exposure to HPHCs and a set of biomarkers of effect indicative of multiple pathophysiological pathways underlying the development of smoking-related diseases. METHODS This multiregional (United States, Japan, and Europe), multicenter (42 sites) cohort study consisting of a 1-year SA period in an ambulatory setting was conducted from May 2015 to May 2017. A total of 1184 male and female adult healthy smokers, willing to quit smoking, were enrolled in the study. Nicotine replacement therapy (NRT) was provided for up to 3 months upon the subject’s request. SC counseling and behavioral support were continuously provided. Biomarkers of exposure to HPHCs and biomarkers of effect were assessed in urine and blood at baseline, Month 3, Month 6, and Month 12. Cardiovascular biomarkers of effect included parameters reflecting inflammation (white blood cell), lipid metabolism (high-density lipoprotein cholesterol), endothelial function (soluble intercellular adhesion molecule-1), platelet function (11-dehydrothromboxane B2), oxidative stress (8-epi-prostaglandin F2 alpha), and carbon monoxide exposure (carboxyhemoglobin). Respiratory biomarkers of effect included lung function parameters and cough symptoms. The biomarkers of effect to evaluate genotoxicity (total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) and xenobiotic metabolism (cytochrome P450 2A6 activity) were also assessed. Continuous SA was verified at each visit following the actual quit date using self-reporting and chemical verification. Safety assessments included adverse events and serious adverse events, body weight, vital signs, spirometry, electrocardiogram, clinical chemistry, hematology and urine analysis safety panel, physical examination, and concomitant medications. RESULTS In total, 1184 subjects (50.1% male) were enrolled; 30% of them quit smoking successfully for 1 year. Data analyses of the study results are ongoing and will be published after study completion. CONCLUSIONS This study provides insights into biological and functional changes and health effects, after continuous SA over 1 year. Study results will be instrumental in assessing novel alternative products to cigarettes considered for tobacco harm reduction strategies. CLINICALTRIAL ClinicalTrials.gov NCT02432729; http://clinicaltrials.gov/ct2/show/NCT02432729 (Archived by WebCite at http://www.webcitation.org/78QxovZrr) INTERNATIONAL REGISTERED REPOR DERR1-10.2196/12138

scholarly journals Rationale, Design, and Methodology of a Prospective Cohort Study for Coping with Behavioral and Psychological Symptoms of Dementia: The RECage Project

2021 ◽  
Vol 80 (4) ◽  
pp. 1613-1627
Author(s):  
Eleni Poptsi ◽  
Magda Tsolaki ◽  
Sverre Bergh ◽  
Bruno Mario Cesana ◽  
Alfonso Ciccone ◽  
...  
Keyword(s):  
Cohort Study ◽  
Psychotropic Drug ◽  
Psychological Symptoms ◽  
Cost Of Care ◽  
Community Dwelling ◽  
Drug Consumption ◽  
Study Results ◽  
Short And Long Term ◽  
Behavioral And Psychological Symptoms

Background: Behavioral and psychological symptoms of dementia (BPSD) are quite challenging problems during the dementia course. Special Care Units for people with dementia (PwD) and BPSD (SCU-B) are residential medical structures, where BPSD patients are temporarily admitted, in case of unmanageable behavioral disturbances at home. Objective: RECage (REspectful Caring for AGitated Elderly) aspires to assess the short and long-term effectiveness of SCU-Bs toward alleviating BPSD and improving the quality of life (QoL) of PwD and their caregivers. Methods: RECage is a three-year, prospective study enrolling 500 PwD. Particularly, 250 community-dwelling PwDs presenting with severe BPSD will be recruited by five clinical centers across Europe, endowed with a SCU-B, for a short period of time; a second similar group of 250 PwD will be followed by six other no-SCU-B centers solely via outpatient visits. RECage’s endpoints include short and long-term SCU-B clinical efficacy, QoL of patients and caregivers, cost-effectiveness of the SCU-B, psychotropic drug consumption, caregivers’ attitude toward dementia, and time to nursing home placement. Results: PwD admitted in SCU-Bs are expected to have diminished rates of BPSD and better QoL and their caregivers are also expected to have better QoL and improved attitude towards dementia, compared to those followed in no-SCU-Bs. Also, the cost of care and the psychotropic drug consumption are expected to be lower. Finally, PwD followed in no-SCU-Bs are expected to have earlier admission to nursing homes. Conclusion: The cohort study results will refine the SCU-B model, issuing recommendations for implementation of SCU-Bs in the countries where they are scarce or non-existent.

scholarly journals Short- and Long-Term Major Cardiovascular Adverse Events in Carotid Artery Interventions: A Nationwide Population-Based Cohort Study in Taiwan

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0121016 ◽  
Author(s):  
Ming-Lung Tsai ◽  
Chun-Tai Mao ◽  
Dong-Yi Chen ◽  
I-Chang Hsieh ◽  
Ming-Shien Wen ◽  
...  
Keyword(s):  
Cohort Study ◽  
Carotid Artery ◽  
Adverse Events ◽  
Population Based ◽  
Short And Long Term

scholarly journals Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results

2021 ◽  
pp. 135245852110379
Author(s):  
Ralf Gold ◽  
Douglas L Arnold ◽  
Amit Bar-Or ◽  
Robert J Fox ◽  
Ludwig Kappos ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Dimethyl Fumarate ◽  
Phase Iii ◽  
Study Results ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background: Dimethyl fumarate (DMF) demonstrated favorable benefit–risk in relapsing-remitting multiple sclerosis (RRMS) patients in phase-III DEFINE and CONFIRM trials, and ENDORSE extension. Objective: The main aim of this study is assessing DMF safety/efficacy up to 13 years in ENDORSE. Methods: Randomized patients received DMF 240 mg twice daily or placebo (PBO; Years 0–2), then DMF (Years 3–10; continuous DMF/DMF or PBO/DMF); maximum follow-up (combined studies), 13 years. Results: By January 2020, 1736 patients enrolled/dosed in ENDORSE (median follow-up 8.76 years (ENDORSE range: 0.04–10.98) in DEFINE/CONFIRM and ENDORSE); 52% treated in ENDORSE for ⩾6 years. Overall, 551 (32%) patients experienced serious adverse events (mostly multiple sclerosis (MS) relapse or fall; one progressive multifocal leukoencephalopathy); 243 (14%) discontinued treatment due to adverse events (4% gastrointestinal (GI) disorders). Rare opportunistic infections, malignancies, and serious herpes zoster occurred, irrespective of lymphocyte count. For DMF/DMF ( n = 501), overall annualized relapse rate (ARR) remained low (0.143 (95% confidence interval (CI), 0.120–0.169)), while for PBO/DMF ( n = 249), ARR decreased after initiating DMF and remained low throughout (ARR 0–2 years, 0.330 (95% CI, 0.266–0.408); overall ARR (ENDORSE, 0.151 (95% CI, 0.118–0.194)). Over 10 years, 72% DMF/DMF and 73% PBO/DMF had no 24-week confirmed disability worsening. Conclusion: Sustained DMF safety/efficacy was observed in patients followed up to 13 years, supporting DMF’s positive benefit/risk profile for long-term RRMS treatment.

scholarly journals СВИНЦОВАЯ ЭКСПОЗИЦИЯ КАК ПРЕДПОСЫЛКА ОГРАНИЧЕНИЯ РЕАЛИЗАЦИИ МАКСИМАЛЬНОЙ ФИЗИЧЕСКОЙ АКТИВНОСТИ

World Science ◽  
2021 ◽  
Author(s):  
Mermanishvili Tatiana ◽  
Pataraia Giorgi ◽  
Chanturidze Nana
Keyword(s):  
Heart Muscle ◽  
Structural Changes ◽  
Clinical Manifestations ◽  
Transport Function ◽  
Long Term Effects ◽  
Functional Changes ◽  
Study Results ◽  
Small Doses ◽  
And Diffusion

As a result of man’s technological activities, numerous quantities of lead and its compounds are spread into the environment annually. The long-term effects of low doses of lead on the lungs, heart muscle and the transport function of erythrocytes were investigated.  The study results indicate that long-term intake of small doses of lead, even in the absence of visible clinical manifestations, causes distinct structural changes and therefore, functional changes in the heart muscle, respiratory system, reduces the transport function of erythrocytes, and also possibly limiting the oxygen transport in myocytes and its deposition in tissues and diffusion into cells. There is no doubt that these changes will limit the ability to maximize the realization of physical activity.

scholarly journals P504 Effectiveness and safety of ustekinumab maintenance therapy in 103 patients with real-world ulcerative colitis: A GETAID multicentre cohort study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S486-S487
Author(s):  
M Fumery ◽  
J Filippi ◽  
V Abitbol ◽  
A Biron ◽  
D Laharie ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Cohort Study ◽  
Adverse Events ◽  
Real World ◽  
Clinical Remission ◽  
Real Life ◽  
Phase Iii ◽  
Phase Iii Trials ◽  
One Year

Abstract Background Phase III trials have demonstrated the efficacy and safety of ustekinumab in moderate-to-severe ulcerative colitis (UC), but no real-life long-term data is currently available. Methods From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined by a partial Mayo Clinic score ≤ 2. The aim of the present study was to assess long-term effectiveness and safety of ustekinumab in UC. Results 103 UC patients (62 men; mean age: 41.2 ± 16.2 years; 52% pancolitis E3) were included in 21 centres. History of immunomodulator, anti-TNF and vedolizumab therapies was noted in 84.5%, 99.0% and 85.4% of the cases, respectively. At week 54, 44 (43%) patients discontinued ustekinumab, for lack of efficacy (n=41), pregnancy (n=1), persistence of eczematiform lesions (n=1) or personal decision (n=1). Cumulative probabilities of ustekinumab persistence were 96.1%, 81.6%, 71.7%, and 58.4% after 3, 6, 9, and 12 months, respectively. In multivariate analysis, a CRP>5 mg/L at week 0 (OR=2.91, CI95%[1.15–7.36]; p=0.02) and concomitant steroids at week 0 (OR=3.05, CI95%[1.30–7.14]; p=0.01) were significantly associated with ustekinumab discontinuation within one year. The overall rate of steroid-free clinical remission at week 52 was 32% of whom 71% had null rectal bleeding and stool frequency subscores. Ten patients (9.7%) underwent colectomy within a median of 6.7 [4.3–10.6] months. Adverse events were observed in 15 (16.9%) patients, of whom 4 (4.5%) had severe adverse events including three patients with exacerbation of UC leading to hospitalization, and a 62 years-old men who died from a myocardial infarction four months after ustekinumab initiation. Conclusion In this real-world cohort study that included patients with refractory ulcerative colitis to multiple therapies, more than one-half of patients were still treated by ustekinumab and one-third were in steroid-free clinical remission, after 52 weeks.

An Ethnographic Investigation Tracking the Experience of Chronic Myeloid Leukemia (CML) Patients on Tyrosine Kinase Inhibitor (TKI) Therapies

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 394-394 ◽  
Author(s):  
François Guilhot ◽  
John Coombs ◽  
Tomasz Szczudlo ◽  
Oleg Zernovak ◽  
Nancy J. Macdonald ◽  
...  
Keyword(s):  
Adverse Events ◽  
Research Funding ◽  
Kinase Inhibitor ◽  
Healthcare Providers ◽  
Work And Family ◽  
Employment Equity ◽  
Study Results ◽  
Equity Ownership ◽  
The Impact

Abstract Abstract 394 Background: The advent and approval of TKIs has dramatically improved the life expectancy of patients with CML. As treatment innovation has transformed CML into a chronically managed disease, we examined the impact of these changes on patients with CML in order to offer recommendations for healthcare providers (HCPs) to better support patients with CML. Method: 50 patients with CML from Brazil, France, Germany, Russia and Spain were included in this ethnographic investigation including: patients within 18 months of diagnosis and on frontline imatinib therapy (n = 20), patients with ongoing frontline treatment (> 18 months to 7 years, n = 20), and patients who were switched to second- or third-line TKI therapies (n = 10). Patients in all 5 countries participated in a 2.5-hour in-home interview, and patients in Brazil and France completed 7-day photo journals and an optional telephone debrief interview. Patients were asked to discuss and write about their perceptions and experiences regarding such issues as adherence, disease knowledge, disease management, and their relationship with HCPs. Result: This global ethnographic investigation generated a 5-stage, patient-centered model emphasizing emotions and experiences throughout the diagnosis, treatment and management of their disease: crisis, hope, adaption, normalcy, and uncertainty. Depending upon their circumstances, these experiential stages were found to be abbreviated or prolonged and influenced by patients having differentiating levels of knowledge about their disease, comfort levels with the treatment and/or their HCPs, as well as different degrees of optimism about their treatment and long-term prognosis. In addition, the study results showed that patients cycle through the various stages of the model throughout the course of their disease. The crisis phase occurred at diagnosis and tended to resolve upon HCP reassurance of the availability of successful treatments. Hope followed crisis when patients were educated about their disease and its treatments and responded to initial therapy. Adaption involved patients adjusting to any physical changes wrought by the disease, treatments, and associated adverse events. As well, they began to psychologically come to terms with the long-term nature of their disease and develop their drug-taking routines and compliance pattern. As patients attained stability in their disease and adapted to changes, a ‘new’ normal returned and patients began to refocus their life away from the disease back to social, work, and family matters. The uncertainty stage was found to be associated with drug resistance, disease progression, newly occurring adverse events, or due to limitations around access to therapy because of public health regulations or personal financial issues. While uncertainty arose for multiple reasons and could occur at any time after patients had advanced through the 4 preceding phases, patients who went through stages of uncertainty most often cycled back to phases of adaption or normalcy once the issues were resolved. Conclusions: Here, we have identified 5 common patient experience stages and we provide recommendations based on patient research for the management of CML. This investigation suggests that HCPs can help patients move through the early stages of crisis and hope by providing reassurance, along with information and resources regarding drug efficacy and product differentiation, while explaining the importance of speed and depth of responses. Once in the adaption/normalcy stages, HCPs should set expectations for the risk/benefits of long-term chronic drug therapy and long-term disease monitoring and continue to support patient compliance and adherence programs while helping patients achieve and maintain a normal lifestyle. Disclosures: Guilhot: Novartis: Equity Ownership, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding. Coombs:Novartis: Employment, Equity Ownership. Szczudlo:Novartis: Employment, Equity Ownership. Zernovak:Novartis: Employment, Equity Ownership. Macdonald:Novartis: Consultancy. Shapiro:Novartis: Consultancy.

Tolerability profile of zolmitriptan (Zomig™ 311C90), a novel dual central and peripherally acting 5HT1B/1D agonist

Cephalalgia ◽  
1997 ◽  
Vol 17 (18_suppl) ◽  
pp. 41-52 ◽  
Author(s):  
Jg Edmeads ◽  
Ds Millson
Keyword(s):  
Clinical Pharmacology ◽  
Adverse Event ◽  
Adverse Events ◽  
Clinical Studies ◽  
Clinical Chemistry ◽  
Dose Range ◽  
Tolerability Profile ◽  
Term Study ◽  
Long Term Study

Zolmitriptan (Zomig™, formerly 311C90) at doses of 0.5–50 mg was administered to 316 unique volunteers in clinical pharmacology studies and 2,750 unique patients in eight clinical studies of acute migraine treatment. Overall, subjects received almost 50,000 doses; 97% of exposures were at doses >2.5 mg. In the clinical pharmacology studies, the overall incidence of subject exposures experiencing at least one adverse event was 52% with zolmitriptan 2.5 mg (28% with placebo). In placebo-controlled studies, the overall incidence of patients with at least one adverse event was dose-dependent for zolmitriptan over the 1–15 mg dose range, e.g. 42% and 46% with 1 and 2.5 mg, respectively and 58% with 5 mg (29% with placebo). Only four serious adverse events attributable to zolmitriptan were reported. In a long-term study, during which 2,058 outpatients treated a total of 31,579 migraine attacks with either one or two zolmitriptan 5 mg doses over a period of up to 1 year, the number of attacks associated with at least one adverse event was similar after one (26%) and two (24%) doses. The majority (59%) of the adverse events reported in this study (59%) occurred within 2 h of dosing, were predominantly mild (59%) or moderate (35%) in intensity, of ≦4 h duration (58%), required no further action (94%). In placebo-controlled studies, the percentage of patients who reported severe adverse events was similar with zolmitriptan 2.5 mg (4%) and placebo (5%). The most frequently reported adverse events with zolmitriptan in the placebo-controlled clinical studies were asthenia, heaviness (other than chest or neck), dry mouth, nausea, dizziness, somnolence, paresthesia and warm sensations. The type and severity of the adverse events was not influenced by gender (although the frequency of reported adverse events was higher in females, as was the case in the placebo group), age, presence of aura prior to the attack, association of migraine with menstruation, concurrent medication, or by the addition of a second zolmitriptan dose. Zolmitriptan showed a similar tolerability profile in the long-term study, in which a low withdrawal rate due to adverse events of 8% was observed. Zolmitriptan was not associated with an increased frequency of central nervous system-related adverse events in a comparative study of sumatriptan, despite pre-clinical and neurophysiological evidence of a dual peripheral and central action of zolmitriptan. Moreover, zolmitriptan doses of 5–20 mg produced no statistically significant effects on objective assessments of psychometric function. Zolmitriptan had no clinically significant effects on blood pressure (even in patients with controlled mild to moderate hypertension or impaired renal function), ECGs (e.g. there was no evidence of ischemic events) or clinical chemistry, hematological or urinalysis measurements. In summary, zolmitriptan is well tolerated, particularly at the recommended dose of 2.5 mg. Zolmitriptan has a well-defined dose-response with 2.5 mg proving highly effective and optimizing the benefit/risk ratio of treatment. Thus, zolmitriptan is well suited as an acute oral treatment for migraine in the outpatient setting.

scholarly journals P548 Efficacy, safety, and pharmacokinetics after switching from infliximab originator to biosimilar SB2 in inflammatory bowel disease patients: A long-term observational, prospective cohort study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S466-S467
Author(s):  
S Fischer ◽  
S Mesfin ◽  
E Klenske ◽  
H Schmitt ◽  
F Vitali ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Cohort Study ◽  
Adverse Events ◽  
Disease Activity ◽  
Bowel Disease ◽  
Patient Visit ◽  
Serious Adverse Events ◽  
Inflammatory Bowel

Abstract Background SB2 is a biosimilar infliximab approved for the treatment of inflammatory bowel disease (IBD) patients. These are the first prospective data investigating long-term efficacy, safety, and pharmacokinetics after switching from infliximab originator to biosimilar SB2 in IBD patients. Methods This is a prospective, observational cohort study of patients that underwent a switch from infliximab originator to biosimilar SB2 in 2017 as part of routine care at the outpatient Clinic for IBD at the University Hospital of Erlangen, Germany. Long-term safety and clinical effectiveness were recorded over a follow-up period of 18-months. Clinical disease activity was assessed by the Harvey–Bradshaw Index (HBI) in Crohn’s disease (CD) and the partial Mayo Score (pMS) in ulcerative colitis (UC) patients. C-reactive protein (CRP) was analyzed at every patient visit, and IFX trough-level (TL) and anti-IFX antibodies (ADA) were measured prior to every SB2 administration, using the Promonitor® tests. The occurrence of adverse events was registered at every patient visit. Results A total of 148 IBD patients (96 CD, 52 UC) was enrolled. The median duration of previous infliximab treatment before the switch was 29 months (range 1.0–110.0). Median disease activity in CD was an HBI of 3 (0–16) at switch (baseline), 2 (0–13) at month 6, 3 (0–15) at month 12 and 2.5 (0–11) at month 18. Median disease activity in UC was a pMS of 0 (0–6) at baseline, 1 (0–4) at month 6, 1 (0–4) at month 12 and 1 (0–5) at month 18. The median TL for all IBD patients was 6.3 mg/ml (0.1–33.7) at baseline, 5.0 mg/ml (0.1–34.3) at month 6, 6.3 mg/ml (0.1–35.8) at month 12 and 5.1 mg/ml (0.1–35.4) at month 18. CRP for all IBD patients was 2.2 mg/l (0.1–45.6) at baseline, 2.2 mg/l (0.1–90.4) at month 6, 2.3 mg/l (0.1–169.5) at month 12 and 2.7 mg/l (0.1–19.8) at month 18. In the 18-month follow-up period, 12/103 (11.7%) of patients who were ADA-negative at baseline developed ADA post-switch. Altogether, 40 (27%) IBD patients discontinued SB2 treatment during the 18-month follow-up period (4 anaphylaxis, 20 loss of response, 7 non-serious and 9 serious adverse events), 2 paused during pregnancy, 1 discontinued in clinical remission, 10 were lost to follow-up (7 change of physician, 3 unknown). Serious adverse events comprised 3 malignancies (breast and prostate carcinoma, neuroendocrine malignancy), 1 liver abscess and 5 intestinal surgical procedures (1 perforation, 1 ileus, and 3 stenoses). Conclusion Switching from IFX originator to biosimilar SB2 was not associated with an increase in disease activity. No clinically meaningful changes in IFX trough levels or immunogenicity were identified. Altogether, SB2 was well tolerated in a real-life setting.

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