| 1. |
|
|
| 2. |
- Baker, K., et al.
(författare)
-
Performance of five pulse oximeters to detect hypoxaemia as an indicator of severe illness in children under five by frontline health workers in low resource settings- A prospective, multicentre, single-blinded, trial in Cambodia, Ethiopia, South Sudan, and Uganda
- 2021
-
Ingår i: Eclinicalmedicine. - : Elsevier BV. - 2589-5370. ; 38
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Low blood oxygen saturation (SpO2), or hypoxaemia, is an indicator of severe illness in children. Pulse oximetry is a globally accepted, non-invasive method to identify hypoxaemia, but rarely available outside higher-level facilities in resource-constrained countries. This study aims to evaluate the performance of different types of pulse oximeters amongst frontline health workers in Cambodia, Ethiopia, South Sudan, and Uganda. Methods: Five pulse oximeters (POx) which passed laboratory testing, out of an initial 32 potential pulse oximeters, were evaluated by frontline health workers for performance, defined as agreement between the SpO2 measurements of the test device and the reference standard. The study protocol is registered with the Australia New Zealand Clinical Trials Registry (Ref: ACTRrn12615000348550). Findings: Two finger-tip pulse oximeters (Contec and Devon), two handheld pulse oximeters (Lifebox and Utech), and one phone pulse oximeter (Masimo) passed the laboratory testing. They were evaluated for performance on 1,313 children under five years old by 207 frontline health workers between February and May 2015. Phone and handheld pulse oximeters had greater overall agreement with the reference standard (56%; 95% CI 0.52 - 0.60 to 68%; 95% CI 0.65 - 0.71) than the finger-tip POx (31%; 95% CI 0.26 to 0.36 and 47%; 95% CI 0.42 to 0.52). Fingertip POx performance was substantially lower in the 0-2 month olds; having just 17% and 25% agreement. The finger-tip devices more often underreported SpO2 readings (mean difference -7.9%; 95%CI -8.6,-7.2 and -3.9%; 95%CI -4.4,-3.4), and therefore over diagnosed hypoxaemia in the children assessed. Interpretation: While the Masimo phone pulse oximeter performed best, all handheld POx with age-specific probes performed well in the hands of frontline health workers, further highlighting their suitability as a screening tool of severe illness. The poor performance of the fingertip POx suggests they should not be used in children under five by frontline health workers. It is essential that POx are performance tested on children in routine settings (in vivo), not only in laboratories or controlled settings (in vitro), before being introduced at scale.
|
|
| 3. |
- Baker, K., et al.
(författare)
-
Performance of Four Respiratory Rate Counters to Support Community Health Workers to Detect the Symptoms of Pneumonia in Children in Low Resource Settings: A Prospective, Multicentre, Hospital-Based, Single-Blinded, Comparative Trial
- 2019
-
Ingår i: EClinicalMedicine. - : Elsevier BV. - 2589-5370.
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Pneumonia is one of the leading causes of death in children under-five globally. The current diagnostic criteria for pneumonia are based on increased respiratory rate (RR) or chest in-drawing in children with cough and/or difficulty breathing. Accurately counting RR is difficult for community health workers (CHWs). Current RR counting devices are frequently inadequate or unavailable. This study analysed the performance of improved RR timers for detection of pneumonia symptoms in low-resource settings. Methods: Four RR timers were evaluated on 454 children, aged from 0 to 59 months with cough and/or difficulty breathing, over three months, by CHWs in hospital settings in Cambodia, Ethiopia, South Sudan and Uganda. The devices were the Mark Two ARI timer (MK2 ARI), counting beads with ARI timer, Rrate Android phone and the Respirometer feature phone applications. Performance was evaluated for agreement with an automated RR reference standard (Masimo Root patient monitoring and connectivity platform with ISA CO2 capnography). This study is registered with ANZCTR [ACTRN12615000348550]. Findings: While most CHWs managed to achieve a RR count with the four devices, the agreement was low for all; the mean difference of RR measurements from the reference standard for the four devices ranged from 0.5 (95% C.I. − 2.2 to 1.2) for the respirometer to 5.5 (95% C.I. 3.2 to 7.8) for Rrate. Performance was consistently lower for young infants (0 to < 2 months) than for older children (2 to ≤ 59 months). Agreement of RR classification into fast and normal breathing was moderate across all four devices, with Cohen's Kappa statistics ranging from 0.41 (SE 0.04) to 0.49 (SE 0.05). Interpretation: None of the four devices evaluated performed well based on agreement with the reference standard. The ARI timer currently recommended for use by CHWs should only be replaced by more expensive, equally performing, automated RR devices when aspects such as usability and duration of the device significantly improve the patient-provider experience. Funding: Bill & Melinda Gates Foundation [ OPP1054367]. © 2019
|
|
| 4. |
- Egg, David, et al.
(författare)
-
Therapeutic options for CTLA-4 insufficiency
- 2022
-
Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 149:2, s. 736-746
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Heterozygous germline mutations in cytotoxic T lymphocyte-associated antigen-4 (CTLA4) impair the immunomodulatory function of regulatory T cells. Affected individuals are prone to life-threatening autoimmune and lymphoproliferative complications. A number of therapeutic options are currently being used with variable effectiveness. Objective: Our aim was to characterize the responsiveness of patients with CTLA-4 insufficiency to specific therapies and provide recommendations for the diagnostic workup and therapy at an organ-specific level. Methods: Clinical features, laboratory findings, and response to treatment were reviewed retrospectively in an international cohort of 173 carriers of CTLA4 mutation. Patients were followed between 2014 and 2020 for a total of 2624 months from diagnosis. Clinical manifestations were grouped on the basis of organ-specific involvement. Medication use and response were recorded and evaluated. Results: Among the 173 CTLA4 mutation carriers, 123 (71%) had been treated for immune complications. Abatacept, rituximab, sirolimus, and corticosteroids ameliorated disease severity, especially in cases of cytopenias and lymphocytic organ infiltration of the gut, lungs, and central nervous system. Immunoglobulin replacement was effective in prevention of infection. Only 4 of 16 patients (25%) with cytopenia who underwent splenectomy had a sustained clinical response. Cure was achieved with stem cell transplantation in 13 of 18 patients (72%). As a result of the aforementioned methods, organ-specific treatment pathways were developed. Conclusion: Systemic immunosuppressants and abatacept may provide partial control but require ongoing administration. Allogeneic hematopoietic stem cell transplantation offers a possible cure for patients with CTLA-4 insufficiency.
|
|
| 5. |
- Lasselin, Julie, et al.
(författare)
-
Lipopolysaccharide Alters Motivated Behavior in a Monetary Reward Task : a Randomized Trial
- 2017
-
Ingår i: Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X .- 1740-634X. ; 42:4, s. 801-810
-
Tidskriftsartikel (refereegranskat)abstract
- Inflammation-induced sickness is associated with a large set of behavioral alterations; however, its motivational aspects remain poorly explored in humans. The present study assessed the effect of lipopolysaccharide (LPS) administration at a dose of 2 ng/kg of body weight on motivation in 21 healthy human subjects in a double-blinded, placebo (saline)-controlled, cross-over design. Incentive motivation and reward sensitivity were measured using the Effort Expenditure for Rewards Task (EEfRT), in which motivation for high-effort/high-reward trials vs low-effort/low-reward trials are manipulated by variations in reward magnitude and,probability to win. Because of the strong interactions between sleepiness and motivation, the role of sleepiness was also determined. As expected, the probability to win predicted the choice to engage in high-effort/high-reward trials; however, this occurred at a greater extent after LPS than after saline administration. This effect was related to the level of sleepiness. Sleepiness increased motivation to choose the high-effort/high-reward mode of response, but only when the probability to win was the highest. LPS had no effect on reward sensitivity either directly or via sleepiness. These results indicate that systemic inflammation induced by LPS administration causes motivational changes in young healthy subjects, which are associated with sleepiness. Thus, despite its association with energy-saving behaviors, sickness allows increased incentive motivation when the effort is deemed worthwhile.
|
|
| 6. |
|
|
| 7. |
- Speakman, John R, et al.
(författare)
-
Oxidative stress and life histories: unresolved issues and current needs.
- 2015
-
Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 5:24, s. 745-757
-
Tidskriftsartikel (refereegranskat)abstract
- Life-history theory concerns the trade-offs that mold the patterns of investment by animals between reproduction, growth, and survival. It is widely recognized that physiology plays a role in the mediation of life-history trade-offs, but the details remain obscure. As life-history theory concerns aspects of investment in the soma that influence survival, understanding the physiological basis of life histories is related, but not identical, to understanding the process of aging. One idea from the field of aging that has gained considerable traction in the area of life histories is that life-history trade-offs may be mediated by free radical production and oxidative stress. We outline here developments in this field and summarize a number of important unresolved issues that may guide future research efforts. The issues are as follows. First, different tissues and macromolecular targets of oxidative stress respond differently during reproduction. The functional significance of these changes, however, remains uncertain. Consequently there is a need for studies that link oxidative stress measurements to functional outcomes, such as survival. Second, measurements of oxidative stress are often highly invasive or terminal. Terminal studies of oxidative stress in wild animals, where detailed life-history information is available, cannot generally be performed without compromising the aims of the studies that generated the life-history data. There is a need therefore for novel non-invasive measurements of multi-tissue oxidative stress. Third, laboratory studies provide unrivaled opportunities for experimental manipulation but may fail to expose the physiology underpinning life-history effects, because of the benign laboratory environment. Fourth, the idea that oxidative stress might underlie life-history trade-offs does not make specific enough predictions that are amenable to testing. Moreover, there is a paucity of good alternative theoretical models on which contrasting predictions might be based. Fifth, there is an enormous diversity of life-history variation to test the idea that oxidative stress may be a key mediator. So far we have only scratched the surface. Broadening the scope may reveal new strategies linked to the processes of oxidative damage and repair. Finally, understanding the trade-offs in life histories and understanding the process of aging are related but not identical questions. Scientists inhabiting these two spheres of activity seldom collide, yet they have much to learn from each other.
|
|
