The epidemic of COVID-19 prompted widespread use of mRNA vaccinations

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Industrial Revolution ◽  
Genetic Diseases ◽  
Phase Iii ◽  
Significant Shift ◽  
Long Term Effects ◽  
The Enlightenment ◽  
Number Of Patients ◽  
Distribution Limits ◽  
Extrahepatic Tissues

COVID-19 challenge resulted in huge expenditure in mRNA-lipid-based nanoparticles (LNPs) manufacturing. Hundreds of billions are produced for human use. This is a significant shift, inconceivable only a year ago. If an LNP platform can traverse thick mucus in patients with respiratory difficulties (such as cystic fibrosis) or target extrahepatic tissues in the future, multi-billion-dose procedures are in place to serve a significant number of patients with unusual genetic diseases (>100,000 individuals). Due to LNPs' versatility in delivering genome editing components, a successful strategy might be easily scaled up and employed to successfully eliminate a rare disease with a single treatment.COVID-19 led to widespread usage of mRNA vaccines. For years, academic and industrial scientists have worked intensely to produce these technologies. Although not enough time to analyze the long-term effects of mRNA vaccines, phase III clinical studies of Pfizer/BioNTech and Moderna vaccines showed around 95 percent efficacy and outstanding safety profiles. The COVID-19 outbreak laid the stage for scaling and overcoming distribution limits that would otherwise have taken decades. RNA treatments and nanomedicine as a field will never be the same again, and will take center stage. The Enlightenment Age of the RNA nanotherapeutics sector is coming to an end, and the area is ready for a full-scale industrial revolution.

scholarly journals Late Effects of High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation (HDT-AHCT) in Elderly Patients with Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4620-4620
Author(s):  
Parastoo B. Dahi ◽  
Chikaodi Obioha ◽  
Sheila Kenny ◽  
Patrick Hilden ◽  
Molly Maloy ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Median Time ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Disease Stage ◽  
High Dose ◽  
Long Term Effects ◽  
Post Transplant ◽  
Number Of Patients

Abstract Background: High-dose chemotherapy and autologous hematopoietic cell transplantation (HDT-AHCT) is an established treatment for non-Hodgkin lymphoma (NHL). Incidence of NHL is highest in patients over 60 years of age, however, limited data is available on long-term effects of HDT-AHCT in older patients. This study is conducted to evaluate the late cardiopulmonary effects and overall outcomes of HDT-AHCT in older patients. Methods: This is a single-center, retrospective study examining late cardiopulmonary effects, and overall outcomes of HDT-AHCT in 41 patients age 70 years and older, with NHL, between January 2000 and December 2016. Clinical data and comorbidities were correlated with outcomes. Pre- and post-transplant pulmonary function tests (PFT) and echocardiograms were compared. Overall survival (OS) and progression-free survival (PFS) were analyzed according to age, gender, disease histology, disease stage at diagnosis, number of lines of treatment, Karnofsky Performance Status (KPS), hemoglobin adjusted diffusing capacity of lungs for carbon monoxide (DLCO), left ventricular ejection fraction (LVEF), and hematopoietic cell transplantation comorbidity index (HCT-CI) at the time of HDT-AHCT. Results: A total of 41 patients underwent HDT-AHCT for follicular or diffuse large B-cell lymphoma (FL / DLBCL n=18 44%), mantle cell lymphoma (MCL n=15 37%) and T-cell or other NHL subtypes (n=8 19%). The median age was 72 (range 70-77). Eight (19%), 6 (15%) and 27 (66%) patients had a low (0), intermediate (1-2) and high (≥3) HCT-CI score, respectively, at transplant. All patients except 1, had received anthracycline as part of initial treatment. BEAM and RR-BEAM were the most common conditioning regimens (n=38 93%). Pre-transplant LVEF was within normal range in all patients except 1 (45%). The median (range) pre- and post-transplant LVEF was 63% (45-74%) and 64% (39-71%), respectively. Of the 23 patients who had a post-transplant echocardiogram (median time between the pre- and post-transplant echocardiogram was 423 days), a mild decrease in LVEF was noted in 3. Only 1 patient had a significant decline of 19% in LVEF. Pulmonary artery pressure (PAP) was within normal range pre- and post-transplant in all. The median (range) of pre-transplant DLCO, FEV1 and FVC were 70% (48-125%), 97% (83-141%), and 98% (57-123%), respectively. Of the 10 patients who underwent post-transplant PFT (median time between the pre- and post-transplant PFT was 405 days), DLCO decline of >10% was the most common abnormality, and developed in 4 out of 10 patients. In 5 patients DLCO improvement of >10% was observed. A greater than 15% improvement in FEV1 and FVC was observed in 5 of 10 and 4 of 10 patients respectively. The median improvements in FVC, FEV1 and DLCO were 4%, 6% and 10%, respectively. With a median follow-up of 58 months (range 5-123) for survivors, PFS and OS at 3 years were 84% (95% CI, 67-92%) and 94% (95% CI, 80-99%), respectively. In a univariate analysis, age, gender, histology, disease stage, number of lines of treatment, DLCO, LVEF, and HCT-CI score did not affect OS or PFS. However, KPS ≥90 was associated with worse OS (p=0.008). The small sample size may have been a contributor to this unexpected finding. Relapse occurred in 11 patients (27%), 8 of whom died. Median time to relapse was 38 months (range 26-100). Secondary malignancies developed in 4 patients (8%) which included acute myeloid leukemia in 2, melanoma in 1, and esophageal cancer in 1, and led to death in 3. Conclusion: In this cohort of elderly patients with NHL who underwent HDT-AHCT, the late declines in cardiopulmonary function were minimal, and none resulted in mortality. Secondary malignancy was the only cause of non-relapse mortality. This can be explained by age being the biggest single risk factor for cancer development in general, in addition to the effects of HDT. We show that the most common cause of long-term mortality after HDT-AHCT continues to be lymphoma recurrence. Our data though limited by small number of patients and its retrospective nature, suggest that age alone is not predictive of post-transplant late effects and outcomes, and therefore should not be used to preclude HDT-AHCT in elderly. While prospective studies with larger number of patients are needed to evaluate long-term effects of HDT-AHCT on different organ functions in older adults, strategies to mitigate risk of relapse remain the most important area to improve outcomes. Disclosures Sauter: Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Precision Biosciences: Consultancy; Kite: Consultancy.

scholarly journals Short and Long-Term Effects of Growth Hormone in Children and Adolescents With GH Deficiency

2021 ◽  
Vol 12 ◽  
Author(s):  
Michael B. Ranke
Keyword(s):  
Gh Deficiency ◽  
Child Growth ◽  
Treatment Modalities ◽  
Diagnostic Process ◽  
Childhood And Adolescence ◽  
Long Term Effects ◽  
Childhood Onset ◽  
Gh Secretion ◽  
Number Of Patients

The syndrome of impaired GH secretion (GH deficiency) in childhood and adolescence had been identified at the end of the 19th century. Its non-acquired variant (naGHD) is, at childhood onset, a rare syndrome of multiple etiologies, predominantly characterized by severe and permanent growth failure culminating in short stature. It is still difficult to diagnose GHD and, in particular, to ascertain impaired GH secretion in comparison to levels in normally-growing children. The debate on what constitutes an optimal diagnostic process continues. Treatment of the GH deficit via replacement with cadaveric pituitary human GH (pit-hGH) had first been demonstrated in 1958, and opened an era of therapeutic possibilities, albeit for a limited number of patients. In 1985, the era of recombinant hGH (r-hGH) began: unlimited supply meant that substantial long-term experience could be gained, with greater focus on efficacy, safety and costs. However, even today, the results of current treatment regimes indicate that there is still a substantial fraction of children who do not achieve adult height within the normal range. Renewed evaluation of height outcomes in childhood-onset naGHD is required for a better understanding of the underlying causes, whereby the role of various factors - diagnostics, treatment modalities, mode of treatment evaluation - during the important phases of child growth - infancy, childhood and puberty - are further explored.

The Atlantic Slave Trade and its Lasting Impact

2018 ◽  
pp. 59-75
Author(s):  
Wasiq Khan
Keyword(s):  
Industrial Revolution ◽  
Slave Trade ◽  
Academic Research ◽  
Long Term Effects ◽  
Slave Labor ◽  
Source Regions ◽  
Transatlantic Trade ◽  
Economic Motives ◽  
Second World

This chapter describes aspects of the transatlantic slave trade specific to regions that now comprise Nigeria and provides a review of academic research since the Second World War on the causes, effects, and character of the trade. Because of its volume, duration, and destabilizing effects, the trade had a profound impact on Nigeria’s political and economic evolution. Modern scholarship has centered around five recurring questions: How large was the trade? How efficient and productive was slave labor relative to free labor? Did the trade catalyze the Industrial Revolution in England? Did the trade retard the long-term economic development of Africa? Why did Africa, as opposed to many other potential source regions, become the New World’s primary provider of slave labor? Despite decades of research and scholarly debate, questions about the economic motives for the transatlantic trade and its long-term effects on Africa’s development remain unsettled.

Health-Related Quality of Life in Long-Term Survivors of Testicular Cancer

2009 ◽  
Vol 27 (35) ◽  
pp. 5993-5999 ◽  
Author(s):  
Philip Blach Rossen ◽  
Anette Fischer Pedersen ◽  
Robert Zachariae ◽  
Hans von der Maase
Keyword(s):  
Quality Of Life ◽  
Testicular Cancer ◽  
University Hospital ◽  
Life Questionnaire ◽  
Long Term Effects ◽  
Number Of Patients ◽  
Health Related ◽  
Long Term Survivors

Purpose A growing number of patients with testicular cancer (TC) become long-term survivors. As a consequence, quality-of-life (QOL) issues become increasingly important. The objective of this study was to investigate QOL among Danish TC survivors. Methods A long-term follow-up assessment of all patients with TC treated at Aarhus University Hospital in Denmark between 1990 and 2000 was conducted. A total of 401 survivors (response rate, 66%) completed questionnaires concerning QOL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30), depression (Beck Depression Inventory-II), fatigue (Multidimensional Fatigue Inventory-20), and health-related issues such as neurotoxic symptoms and Raynaud-like phenomena. On the basis of their treatment, participants were categorized as having received surveillance, radiotherapy, or chemotherapy. Results QOL among patients with TC was equal to that of men from the general population. Although patients who received chemotherapy reported higher levels of peripheral sensory neuropathy, ototoxicity, and Raynaud-like phenomena, treatment strategies were generally unrelated to QOL and depressive symptoms. Conclusion Overall, the patients in this study reported high levels of QOL. The results suggest that patients treated for TC should be informed about the anticipated good post-therapeutic QOL and the low risk of psychosocial and physical long-term effects.

Physical Health of Members of the Public Who Experienced Terrorist Bombings in London on 07 July 2005

2010 ◽  
Vol 25 (2) ◽  
pp. 139-144 ◽  
Author(s):  
Michael A. Catchpole ◽  
Oliver Morgan
Keyword(s):  
Physical Health ◽  
Health Effects ◽  
Response Rate ◽  
Long Term Effects ◽  
Health Symptoms ◽  
The Public ◽  
Number Of Patients ◽  
London Bombings

AbstractIntroduction:On 07 July 2005, four bombs were detonated in London, killing 52 members of the public. Approximately 700 individuals received treatment either at the scene or at nearby hospitals.Hypothesis/Problem:Significant concerns about the potential long-term psychological and physical health effects of exposure to the explosions were raised immediately after the bombings. To address these concerns, a public health register was established for the purpose of following-up with individuals exposed to the explosions.Methods:Invitations to enroll in the register were sent to individuals exposed to the explosions. A range of health, emergency, and humanitarian service records relating to the response to the explosions were used to identify eligible individuals. Follow-up was undertaken through self-administered questionnaires. The number of patients exposed to fumes, smoke, dust, and who experienced blood splashes, individuals who reported injuries, and the type and duration of health symptoms were calculated. Odds ratios of health symptoms by exposure for greater or less than 30 minutes were calculated.Results:A total of 784 eligible individuals were identified, of whom, 258 (33%) agreed to participate in the register, and 173 (22%) returned completed questionnaires between 8 to 23 months after the explosions. The majority of individuals reported exposure to fumes, smoke, or dust, while more than two-fifths also reported exposure to blood. In addition to cuts and puncture wounds, the most frequent injury was ear damage. Most individuals experienced health symptoms for less than four weeks, with the exception of hearing problems, which lasted longer. Four-fifths of individuals felt that they had suffered emotional distress and half of them were receiving counseling.Conclusions:The results indicated that the main long-term health effects, apart from those associated with traumatic amputations, were hearing loss and psychological disorders. While these findings provide a degree of reassurance of the absence of long-term effects, the low response rate limits the extent to which this can be extrapolated to all those exposed to the bombings. Given the importance of immediate assessment of the range and type of exposure and injury in incidents such as the London bombings, and the difficulties in contacting individuals after the immediate response phase, there is need to develop better systems for identifying and enrolling exposed individuals into post-incident health monitoring.

scholarly journals A Functional Threshold for Long-Term Use of Hand and Arm Function Can Be Determined: Predictions From a Computational Model and Supporting Data From the Extremity Constraint-Induced Therapy Evaluation (EXCITE) Trial

2009 ◽  
Vol 89 (12) ◽  
pp. 1327-1336 ◽  
Author(s):  
Nicolas Schweighofer ◽  
Cheol E. Han ◽  
Steven L. Wolf ◽  
Michael A. Arbib ◽  
Carolee J. Winstein
Keyword(s):  
Controlled Trial ◽  
Hand Function ◽  
Cost Effective ◽  
Phase Iii ◽  
Future Research ◽  
Therapy Evaluation ◽  
Effective Interventions ◽  
Term Change ◽  
Number Of Patients

Background Although spontaneous use of the more-affected arm and hand after stroke is an important determinant of participation and quality of life, a number of patients exhibit decreases in use following rehabilitative therapy. A previous neurocomputational model predicted that if the dose of therapy is sufficient to bring performance above a certain threshold, training can be stopped. Objective The aim of this study was to test the hypothesis that there exists a threshold for function of the paretic arm and hand after therapy. If function is above this threshold, spontaneous use will increase in the months following therapy. In contrast, if function is below this threshold, spontaneous use will decrease. Methods New computer simulations are presented showing that changes in arm use following therapy depend on a performance threshold. This prediction was tested by reanalyzing the data from the Extremity Constraint-Induced Therapy Evaluation (EXCITE) trial, a phase III randomized controlled trial in which participants received constraint-induced movement therapy for 2 weeks and were tested both 1 week and 1 year after therapy. Results The results demonstrate that arm and hand function measured immediately after therapy predicts, on average, the long-term change of arm use. Above a functional threshold, use improves. Below this threshold, use decreases. Limitations The reanalysis of the EXCITE trial data provides a “group” threshold above which a majority of patients, but not all, improve spontaneously. A goal of future research is to provide the means to assess when patients reach their individual threshold. Conclusion Understanding of the causal and nonlinear relationship between limb function and daily use is important for the future development of cost-effective interventions and prevention of “rehabilitation in vain.”

Of ‘Little People’ and Ancient Monuments

1995 ◽  
Vol 2 (1) ◽  
pp. 30-32 ◽  
Author(s):  
Ton Lemaire
Keyword(s):  
Industrial Revolution ◽  
Specific Area ◽  
Sacred Places ◽  
Funerary Monuments ◽  
Cultural Biography ◽  
The Enlightenment ◽  
Modem World ◽  
Surrounding Landscape ◽  
Ancient Monuments

Roymans' article is an original and valuable contribution to an interpretation of the ‘cultural biography’ of the landscape of a specific area by combining archaeological and folkloric evidence. His study concentrates on the sacred places of this landscape, especially the urnfields and barrows, because ‘these are focal points from which local communities order and interpret the surrounding landscape’. The author rightly stresses that funerary monuments not only had a certain significance in the societies that constructed and used them, but that they also had a prominent place in the landscape of later societies up until pre-modern times. He suggests that, in the Meuse-Demer-Scheldt region, there has been ‘a long-term incorporation of prehistorical burial monuments in the mythical landscape of later inhabitants’. Archaeology itself, for that matter, should be understood in the perspective of the (dis)continuing biography of the landscape because it presupposes the destruction of the ancient mythical geography, including the Christian one. Archaeology is the product of the ‘modernisation’ of space: it is presupposing and reflecting (upon) the coming of the modem world with its rationalisation and Entzauberung (disenchantment) of the landscape. In a similar way the study of folklore (Volkskunde in both Dutch and German) has been made possible and interesting by the waning of rural popular culture as a consequence of both the Enlightenment and the industrial revolution. Thus, it is no accident that modernity produced the conditions of becoming aware of the mythical meaning of the landscape exactly at the time that its traces are disappearing in the physical landscape as well as in the memory of the rural population.

scholarly journals Post COVID-19 sequelae: A prospective observational study from Northern India

2021 ◽  
Author(s):  
Shivdas Rajaram Naik ◽  
Manish Soneja ◽  
Soumendra Haldar ◽  
Netto George Mundadan ◽  
Prerna Garg ◽  
...  
Keyword(s):  
Observational Study ◽  
Prospective Observational Study ◽  
Long Term Effects ◽  
Northern India ◽  
The North ◽  
Disturbed Sleep ◽  
Number Of Patients ◽  
Tertiary Healthcare ◽  
Severity Of The Disease

Background: Long COVID, or post-COVID-19 sequelae, is being seen in a growing number of patients reporting a constellation of symptoms, both pulmonary and extrapulmonary. Studies on COVID-19 recovered patients are scarce. Thus, there is a need to add granularity to our existing knowledge about the course and long-term effects of the infection. Aim: To describe the clinical details and risk factors of post-COVID sequelae in the North Indian population. Method: This prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 to February 2021. Patients aged >18 years with a confirmed COVID-19 disease were recruited after at least two weeks of diagnosis and interviewed for any post-COVID-19 symptoms. Results: Of 1234 patients recruited, who were followed up for a median duration of 91 days (IQR: 45-181 days), 495 (40.11%) patients had symptoms. In 223 (18.1%) patients, the symptoms resolved within four weeks, 150 (12.1%) patients had symptoms till twelve weeks, and 122 (9.9%) patients had symptoms beyond twelve weeks of diagnosis of COVID-19. Most common long COVID-19 symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), disturbed sleep (1.4%), mood disturbances (0.48%) and anxiety (0.6%). The major determinants of developing post-COVID-19 symptoms in the patients were hypothyroidism and the severity of the disease. Conclusion: Most often, patients complain of myalgias, fatigue, dyspnoea, cough and disturbed sleep. Patients who are hypothyroid or have recovered from moderate to severe COVID-19 are at higher risk of developing post-COVID sequelae. Therefore, a multidisciplinary approach is required to diagnose and manage COVID-19 recovered patients.

scholarly journals Alveolar Bone Resorption Evaluation Around Single-piece Designed Bicortical Implants, Using Immediate Loading Protocol, Based on Orthopantomographs

2017 ◽  
Vol 2 (4) ◽  
pp. 328-331 ◽  
Author(s):  
Dániel-Tamás Száva ◽  
Alina Ormenișan ◽  
Emese Markovics ◽  
Bálint Bögözi ◽  
Krisztina Mártha
Keyword(s):  
Bone Resorption ◽  
Dental Implants ◽  
Alveolar Bone ◽  
Implant Design ◽  
Immediate Loading ◽  
Long Term Effects ◽  
Number Of Patients ◽  
Functional Loading ◽  
Short Diameter

AbstractBackground:Inserting dental implants in severely atrophied jawbones is a great challenge for the dental practitioner. There are an increasing number of patients who choose dental implantanchored prosthetic restorations despite compromised bone quality and quantity. There have been numerous attempts in adapting implant design for the atrophic crestal bone. One-piece, needle-type basal implant design is a typical design for these cases. These implants are inserted in the remaining compact bone located in the basal aspect of the jawbones. If high primary stability is achieved, these implants are used for immediate loading protocol. From many points of view, this technique is based on contradictory principles compared to classic implant surgery and loading protocols. Theaimof this study was to investigate the long-term success of basal one-piece short-diameter dental implants used for immediate loading protocol.Materials and methods:A total of 56 dental implants were included in this study. Peri-implant bone loss was measured on orthopantomographs. Bone resorption was measured in millimeters in the first 6 and 12 months of functional loading.Results:There were no failing implants in this period; average bone resorption was 1.59 mm after 6 months of functional loading and 2.05 mm after 12 months. Bone resorption was slightly higher in the mandible than in the maxilla.Conclusions:Immediate implant loading protocol might be an attractive solution for fixed fullarch restoration using short-diameter one-stage basal implants, but long-term effects require further investigations.

Effects of carotid artery stenosis treatment on blood pressure

2012 ◽  
Vol 117 (4) ◽  
pp. 755-760 ◽  
Author(s):  
Joonho Chung ◽  
Byung Moon Kim ◽  
Ho Kyu Paik ◽  
Dong-Keun Hyun ◽  
Hyeonseon Park
Keyword(s):  
Blood Pressure ◽  
Carotid Artery ◽  
Carotid Artery Stenosis ◽  
Carotid Artery Stenting ◽  
Artery Stenosis ◽  
Percentage Change ◽  
Long Term Effects ◽  
Number Of Patients

Object The purpose of this study was to evaluate and compare the long-term effects of carotid endarterectomy (CEA) and carotid artery stenting (CAS) on blood pressure (BP). Methods Between January 2003 and December 2009, 134 patients underwent 145 procedures for treatment of carotid artery stenosis. Patients with at least 1 year of clinical and radiographic follow-up after treatment were included in this study. A total of 102 patients met this criterion and were placed in the CEA group (n = 59) or the CAS group (n = 43) according to their treatment. The percentage change in BP decrement and the number of patients with a normotensive BP were evaluated and compared between the groups. Results There were no significant differences between the groups with regard to baseline characteristics. Compared with the pretreatment BP, the follow-up BPs were significantly decreased in both groups. At the 1-year followup, the percentage change in the BP decrement was greater in the CAS group (percentage change: systolic BP 9.6% and diastolic BP 12.8%) than in the CEA group (percentage change: systolic BP 5.9% [p = 0.035] and diastolic BP = 8.1% [p = 0.049]), and there were more patients with a normotensive BP in the CAS group (46.5%) than in the CEA group (22.0%, p = 0.012). Conclusions Both CEA and CAS have BP-lowering effects. Carotid artery stenting seems to have a better effect than CEA on BP at the 1-year follow-up.

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