scholarly journals Factors that influence clinical efficacy of live biotherapeutic products

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Bruno Pot ◽  
Yvan Vandenplas

AbstractTraditional probiotics are increasingly being used in a medical context. The use of these products as drugs is considerably different from the traditional use as food or food supplements, as, obviously, the target population is different (diseased versus healthy or at risk population). Besides the target population, also the regulatory context is different, mainly with respect to production, administration regime and type of clinical studies required. In this paper we will, besides the regulatory differences, focus on aspects that may impact the efficacy of a live biotherapeutic product (drug), especially in a clinical setting. The impact of the dosage seems to depend on the strain and the application and may follow some rationale. In contrast, information on the impact of the time of administration or diet, is often still lacking. The matrix and the use of protective measures may clearly have an impact on the survival and efficacy of the strain.

2020 ◽  
Vol 38 (7A) ◽  
pp. 960-966
Author(s):  
Aseel M. Abdullah ◽  
Hussein Jaber ◽  
Hanaa A. Al-Kaisy

In the present study, the impact strength, flexural modulus, and wear rate of poly methyl methacrylate (PMMA) with eggshell powder (ESP) composites have been investigated. The PMMA used as a matrix material reinforced with ESP at two different states (including untreated eggshell powder (UTESP) and treated eggshell powder (TESP)). Both UTESP and TESP were mixed with PMMA at different weight fractions ranged from (1-5) wt.%. The results revealed that the mechanical properties of the PMMA/ESP composites were enhanced steadily with increasing eggshell contents. The samples with 5 wt.% of UTESP and TESP additions give the maximum values of impact strength, about twice the value of the pure PMMA sample. The calcination process of eggshells powders gives better properties of the PMMA samples compared with the UTESP at the same weight fraction due to improvements in the interface bond between the matrix and particles. The wear characteristics of the PMMA composites decrease by about 57% with increases the weight fraction of TESP up to 5 wt.%. The flexural modulus values are slightly enhanced by increasing of the ESP contents in the PMMA composites.


BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e046537
Author(s):  
Sheera Sutherland ◽  
Kirsty E Durley ◽  
Kirsty Gillies ◽  
Margaret Glogowska ◽  
Daniel S Lasserson ◽  
...  

ObjectiveTo explore the impact of the death of a patient in the haemodialysis unit on fellow patients.MethodsWe interviewed patients on dialysis in a tertiary dialysis centre using semistructured interviews. We purposively sampled patients who had experienced the death of a fellow patient. After interviews were transcribed, they were thematically analysed by independent members of the research team using inductive analysis. Input from the team during analysis ensured the rigour and quality of the findings.Results10 participants completed the interviews (6 females and 4 males with an age range of 42–88 years). The four core themes that emerged from the interviews included: (1) patients’ relationship to haemodialysis, (2) how patients define the haemodialysis community, (3) patients’ views on death and bereavement and (4) patients’ expectations around death in the dialysis community. Patients noticed avoidance behaviour by staff in relation to discussing death in the unit and would prefer a culture of open acknowledgement.ConclusionStaff acknowledgement of death is of central importance to patients on haemodialysis who feel that the staff are part of their community. This should guide the development of appropriate bereavement support services and a framework that promotes the provision of guidance for staff and patients in this unique clinical setting. However, the authors acknowledge the homogenous sample recruited in a single setting may limit the transferability of the study. Further work is needed to understand diverse patient and nurse experiences and perceptions when sharing the knowledge of a patient’s death and how they react to loss.


2021 ◽  
Vol 13 ◽  
pp. 1759720X2110026
Author(s):  
Chinar R. Parikh ◽  
Jaya K. Ponnampalam ◽  
George Seligmann ◽  
Leda Coelewij ◽  
Ines Pineda-Torra ◽  
...  

The treatment of inflammatory arthritis has been revolutionised by the introduction of biologic treatments. Many biologic agents are currently licensed for use in both paediatric and adult patients with inflammatory arthritis and contribute to improved disease outcomes compared with the pre-biologic era. However, immunogenicity to biologic agents, characterised by an immune reaction leading to the production of anti-drug antibodies (ADAs), can negatively impact the therapeutic efficacy of biologic drugs and induce side effects to treatment. This review explores for the first time the impact of immunogenicity against all licensed biologic treatments currently used in inflammatory arthritis across age, and will examine any significant differences between ADA prevalence, titres and timing of development, as well as ADA impact on therapeutic drug levels, clinical efficacy and side effects between paediatric and adult patients. In addition, we will investigate factors associated with differences in immunogenicity across biologic agents used in inflammatory arthritis, and their potential therapeutic implications.


2020 ◽  
Vol 11 ◽  
pp. 215145932098036
Author(s):  
David W. Barton ◽  
C. Taylor Smith ◽  
Amit S. Piple ◽  
Sterling A. Moskal ◽  
Jonathan J. Carmouche

Introduction: Osteoporosis is often not clinically recognized until after a fracture occurs. Individuals who have 1 fracture are at increased risk of future fractures. Prompt initiation of osteoporosis treatment following fracture is critical to reducing the rate of future fractures. Antiresorptives are the most widely used class of medications for the prevention and treatment of osteoporosis. Many providers are hesitant to initiate antiresorptives in the acute post-fracture period. Concerns include interference with bone remodeling necessary for successful fracture healing, which would cause increased rates of non-union, malunion, and refracture. While such concerns should not extend to anabolic medications, physicians may also hesitate to initiate anabolic osteoporosis therapies due to high cost and/or lack of familiarity. This article aims to briefly review the available data and present a digestible narrative summary to familiarize practicing orthopaedic surgeons with the essential details of the published research on this topic. Results: The results of 20 clinical studies and key pre-clinical studies related to the effect of anti-resorptive medications for osteoporosis on fracture healing are summarized in the body of this narrative review. Discussion & Conclusions: While few level I studies have examined the impact of timing of initiation of osteoporosis medications in the acute post-fracture period, the few that have been published do not support these concerns. Specifically, data from level I clinical trials indicate that initiating bisphosphonates as early as 2 weeks post-fracture does not increase rates of non-union or malunion. By reviewing the available data, we hope to give clinicians the confidence to initiate osteoporosis treatment promptly post-fracture.


Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 188
Author(s):  
Małgorzata Makarewicz ◽  
Iwona Drożdż ◽  
Tomasz Tarko ◽  
Aleksandra Duda-Chodak

This review presents the comprehensive knowledge about the bidirectional relationship between polyphenols and the gut microbiome. The first part is related to polyphenols’ impacts on various microorganisms, especially bacteria, and their influence on intestinal pathogens. The research data on the mechanisms of polyphenol action were collected together and organized. The impact of various polyphenols groups on intestinal bacteria both on the whole “microbiota” and on particular species, including probiotics, are presented. Moreover, the impact of polyphenols present in food (bound to the matrix) was compared with the purified polyphenols (such as in dietary supplements) as well as polyphenols in the form of derivatives (such as glycosides) with those in the form of aglycones. The second part of the paper discusses in detail the mechanisms (pathways) and the role of bacterial biotransformation of the most important groups of polyphenols, including the production of bioactive metabolites with a significant impact on the human organism (both positive and negative).


2021 ◽  
pp. 1-8
Author(s):  
S. Melker Hagsäter ◽  
Robert Pettersson ◽  
Axel Holmäng ◽  
Elias Eriksson

Abstract Objective: Whereas numerous experimental and clinical studies suggest a complex involvement of serotonin in the regulation of anxiety, it remains to be clarified if the dominating impact of this transmitter is best described as anxiety-reducing or anxiety-promoting. The aim of this study was to assess the impact of serotonin depletion on acquisition, consolidation, and expression of conditioned fear. Methods: Male Sprague–Dawley rats were exposed to foot shocks as unconditioned stimulus and assessed with respect to freezing behaviour when re-subjected to context. Serotonin depletion was achieved by administration of a serotonin synthesis inhibitor, para-chlorophenylalanine (PCPA) (300 mg/kg daily × 3), (i) throughout the period from (and including) acquisition to (and including) expression, (ii) during acquisition but not expression, (iii) after acquisition only, and (iv) during expression only. Results: The time spent freezing was significantly reduced in animals that were serotonin-depleted during the entire period from (and including) acquisition to (and including) expression, as well as in those being serotonin-depleted during either acquisition only or expression only. In contrast, PCPA administrated immediately after acquisition, that is during memory consolidation, did not impact the expression of conditioned fear. Conclusion: Intact serotonergic neurotransmission is important for both acquisition and expression of context-conditioned fear.


2020 ◽  
Vol 4 (1) ◽  
pp. 50-58
Author(s):  
Matthias  Tietsch ◽  
Amir Muaremi ◽  
Ieuan Clay ◽  
Felix Kluge ◽  
Holger Hoefling ◽  
...  

Analyzing human gait with inertial sensors provides valuable insights into a wide range of health impairments, including many musculoskeletal and neurological diseases. A representative and reliable assessment of gait requires continuous monitoring over long periods and ideally takes place in the subjects’ habitual environment (real-world). An inconsistent sensor wearing position can affect gait characterization and influence clinical study results, thus clinical study protocols are typically highly proscriptive, instructing all participants to wear the sensor in a uniform manner. This restrictive approach improves data quality but reduces overall adherence. In this work, we analyze the impact of altering the sensor wearing position around the waist on sensor signal and step detection. We demonstrate that an asymmetrically worn sensor leads to additional odd-harmonic frequency components in the frequency spectrum. We propose a robust solution for step detection based on autocorrelation to overcome sensor position variation (sensitivity = 0.99, precision = 0.99). The proposed solution reduces the impact of inconsistent sensor positioning on gait characterization in clinical studies, thus providing more flexibility to protocol implementation and more freedom to participants to wear the sensor in the position most comfortable to them. This work is a first step towards truly position-agnostic gait assessment in clinical settings.


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