This review discusses the presentation and management of acute sickle crises, highlighting which aspects of diagnosis and management can be undertaken in the community and which require urgent ...referral to hospital. GP's, community nurse specialists, and community paediatricians should be aware of the different acute presentations in order to provide effective and safe care, and should understand warning symptoms and signs which indicate the need for assessment in hospital. It is also important that the parents have a good awareness of these symptoms and know when and how to seek help. The common complications which may be encountered in an acute hospital setting are described together with recommendations for management based on published evidence and the author's experience.
Viral loads were investigated in SIVmnd-1 chronically infected mandrills and the results were compared with those previously observed in other nonpathogenic natural SIV infections. Four naturally and ...11 experimentally SIVmnd-1-infected mandrills from a semi-free-ranging colony were studied during the chronic phase of infection. Four SIVmnd-1-infected wild mandrills were also included for comparison. Twelve uninfected mandrills were used as controls. Viral loads in all chronically infected mandrills ranged from 10
5 to 9 × 10
5 copies/ml and antibody titers ranged from 200 to 14,400 and 200 to 12,800 for anti-V3 and anti-gp36, respectively. There were no differences between groups of wild and captive mandrills. Both parameters were stable during the follow-up, and no clinical signs of immune suppression were observed. Chronic SIVmnd-1-infected mandrills presented slight increases in CD20
+ and CD28
+ /CD8
+ cell counts, and a slight decrease in CD4
+ /CD3
+ cell counts. A slight CD4
+ /CD3
+ cell depletion was also observed in old uninfected controls. Similar to other nonpathogenic models of lentiviral infection, these results show a persistent high level of SIVmnd-1 replication during chronic infection of mandrills, with minimal effects on T cell subpopulations.
Background Voxelotor is a haemoglobin oxygen-affinity modulator that leads to inhibited red blood cell sickling, has demonstrated reduced markers of haemolysis and anaemia improvement, and is one of ...a small number of novel disease-modifiers approved in the US for sickle cell disease (SCD) treatment. It has marketing authorisation in the UK and is currently undergoing reimbursement appraisal. The modelled impact of voxelotor on health-related quality of life (HRQoL)remains a key issue in current trial evidence. Therefore, the need for real-world data and understanding of patient-reported outcomes and experiences following treatment remains critical. Aims This work sought to characterise the side effects, HRQoL, and wearable-captured sleep and activity metrics of SCD patients in the UK, before and after treatment initiation. Methods Feedback from 19 SCD patients who had received voxelotor was captured through an online survey (Aug 2022-Mar 2023). 15 of these patients were also consented and enrolled within an artificial intelligence (AI) platform of over 600 SCD patients that combined genomic, medical record, real-time wearable biometric, and patient-reported outcomes data into a single platform. This included a mobile phone app for day-to-day QoL questionnaire (EQ-5D-5L) entry and an FDA-cleared smartwatch to capture sleep quality and physical activity. Convenience sampling selected data for a 17-patient (89%) subcohort with available pre- and post-voxelotor initiation EQ-5D-5L scores, either through the platform or follow-up survey snapshots. For each patient, this was analysed up to the date on which they completed the survey. EQ-5D-5L was also analysed in comparison to platform patients who had hydroxyurea (HU) in the past (n=19) or were receiving HU at the time of analysis (n=60), in addition to those with no recorded HU use (n=116). Additional analysis compared pre- and post-initiation activity levels (n=6), 4 of whom also had sleep quality data. Results The 19 surveyed patients had received voxelotor for a mean ± SD (range) of 194 ± 415 (17-1,826) days. 11 (58%) had also received HU and 1 (5%) received crizanlizumab. The mean age was 33 ± 13 (14-52) years, 12 (63%) were male, and 16 (84%) had HbSS. Side effects were reported in 8 (42%) patients, mostly diarrhea (6, 32%), stomach pains (2, 11%), and nausea/vomiting (2, 11%). Comparison of the 17-patient pre- to post-voxelotor cohort showed a statistically significant (p<0.001) increase in pooled EQ-5D-5L scores, from 0.558 ± 0.314 to 0.761 ± 0.262 (Figure 1). Post-initiation EQ-5D-5L for these 17 patients was significantly higher than for those receiving HU at 0.731 ± 0.232 (p=0.023) or who had previously received HU at 0.704 ± 0.256 (p=0.040) (Figure 2). Analysis of pre- and post-initiation wearables data saw increased deep sleep in 50% (2/4) and decreased nightly wakeups in 50% (2/4) of patients. Pooled pre- and post-initiation data showed a significant difference in deep sleep (43% vs. 47%, p=0.011). The mean number of steps and distance increased for 50% (3/6) of patients. While soft activity (Metabolic Equivalent of Task (METs): <3, e.g., sleeping, sitting quietly, slow walk) decreased for 67% (4/6) of patients, moderate activity (MET: 3-6, e.g., fast walk, cleaning, gardening) increased in 67% (4/6) and intense activity (MET: >6, e.g., running, hiking) increased in 60% (3/5). Conclusions Our data present a different lens to the voxelotor treatment experience of patients in the UK, with a side effect profile similar to that of other published studies. We demonstrated that EQ-5D-5L increased by 0.203 pre- to post-initiation, and was 0.030 and 0.057 higher than those receiving HU and those who had previously received HU, respectively, in the voxelotor-treated group. These are in line with the ranges of minimally important differences (0.030-0.098) reported for the EQ-5D-5L in other chronic diseases. As such and despite the limitations of small sample size and variability in pre- to post-initiation changes, a statistically significant improvement in HRQoL was observed after initiating voxelotor, as well as in comparison to HU treatment pathways. Similarly, pre- and post-initiation wearables data demonstrated early positive trends in voxelotor's impacts on sleep and activity using an FDA-cleared device, highlighting a need for further research into these metrics and the impact of SCD-modifying treatment.
•Genotype heat stress response evaluated over multiple representative environments.•Demonstrated ability for breeders to evaluate stress tolerance in breeding trials.•Evaluation of stress response at ...multiple growth stages possible in field trials.•Field adaptation is supported by controlled environment phenotyping.
Heat stress is a major constraint on wheat (Triticum aestivum L.) production in many regions of the world. While research into heat stress tolerance has been conducted across many crop species, there are still significant gaps in our understanding of the impacts of heat stress on production, the level of genetic variation for heat stress tolerance in the field and the varying phenotypic responses to various yield components. Here, we report on the heat stress tolerance for 24 bread wheat (Triticum aestivum L.) genotypes which were evaluated across 13-environments over two growing seasons in the Mediterranean-type climate of southern Australia. Numerous climatic co-variates were measured to further understand interactions of temperature stress on crop performance. Not surprisingly, heat stress was found to have significant negative impacts on grain yield in field conditions, with reductions of 302 kg ha−1 ᵒC-1 for each day with maximum temperature in excess of 30ᵒC during anthesis and a reduction of 161 kg ha−1 ᵒC-1 for each day with maximum temperature in excess of 30ᵒC during grain fill. Genotype by environment interactions for grain yield performance under varying levels of heat stress were also observed in the field, suggesting that plant breeding selection strategies could be used to improve adaptation to heat stress. Additionally, all genotypes were phenotyped using a controlled environment assay (plants exposed to an air temperature of 36ᵒC and a wind speed of 40 km h−1 for three consecutive, eight-hour days, 10 days post the end of anthesis). Significant differences in genotype performance for leaf senescence and leaf chlorophyll content in response to heat stress were identified under the controlled environment conditions. Further evaluation showed that some of the field genotype by environment interaction for heat stress tolerance could be explained by performance under controlled environment conditions. This suggests that detailed physiological studies in controlled environment conditions do relate to performance in field conditions.
Summary
A retrospective cohort analysis to explore 10‐year mortality and prevalence of transfusion‐dependent β‐thalassaemia (TDT)‐associated co‐morbidities in patients with TDT was undertaken using ...Hospital Episode Statistics (HES) data from the National Health Service (NHS) in England. A 10‐year forward‐looking cohort analysis for the period 2009–2018 was completed using HES admitted patient care (APC), outpatient data, and linked HES/Office of National Statistics mortality data for patients with β‐thalassaemia (ICD‐10 diagnosis code D56.1). TDT‐associated co‐morbidity rates were high in the 612 patients with TDT, with 76% having at least one co‐morbidity, 54% suffering from two of more, and 37% three or more. The three most common TDT‐associated co‐morbidities, occurring in more than one third of patients were: endocrine disorders (excluding diabetes) 40%, osteoporosis 40%, and diabetes 34%. Cardiac disease was observed in 18% of patients overall, with atrial fibrillation and heart failure being the most common with a prevalence of 11% and 9%, respectively. The crude 10‐year mortality rate in the TDT cohort was 6·2% (38/612), significantly greater than the 1·2% age/sex‐adjusted mortality rate of the general population (P < 0·001). These data support the notion that the unmet need in TDT remains significant, with high rates of co‐morbidity and mortality.
Long-term follow-up of cohorts of patients treated in high-income countries has shown a progressive improvement in life expectancy. Myocardial toxicity from iron overload has been the major cause of ...mortality; however, there has been a substantial decline in cardiac deaths in recent years, related to switching high-risk patients from subcutaneous desferrioxamine to chelation regimes which include the oral chelator deferiprone. The role of deferasirox in enhancing life expectancy is yet to be determined, but it is reasonable to expect an improvement compared with past experience with desferrioxamine. Other causes of mortality will become an increasingly important issue for older thalassemic patients: Surveillance, prophylaxis, and prompt treatment of infection remains essential, and chronic hepatitis virus infection should be managed with best available current therapies. More data on follow-up of thalassemic patients in middle income countries are needed to demonstrate a similar trend in improved survival. The life expectancy for those in low-income countries is similar to the situation 50 years ago in Europe and the United States. The global thalassemia and public health community should consider how to respond to this disparity.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Key message
Assessing adaptation to abiotic stresses such as high temperature conditions across multiple environments presents opportunities for breeders to target selection for broad adaptation and ...specific adaptation.
Adaptation of wheat to heat stress is an important component of adaptation in variable climates such as the cereal producing areas of Australia. However, in variable climates stress conditions may not be present in every season or are present to varying degrees, at different times during the season. Such conditions complicate plant breeders’ ability to select for adaptation to abiotic stress. This study presents a framework for the assessment of the genetic basis of adaptation to heat stress conditions with improved relevance to breeders’ selection objectives. The framework was applied here with the evaluation of 1225 doubled haploid lines from five populations across six environments (three environments selected for contrasting temperature stress conditions during anthesis and grain fill periods, over two consecutive seasons), using regionally best practice planting times to evaluate the role of heat stress conditions in genotype adaptation. Temperature co-variates were determined for each genotype, in each environment, for the anthesis and grain fill periods. Genome-wide QTL analysis identified performance QTL for stable effects across all environments, and QTL that illustrated responsiveness to heat stress conditions across the sampled environments. A total of 199 QTL were identified, including 60 performance QTL, and 139 responsiveness QTL. Of the identified QTL, 99 occurred independent of the 21 anthesis date QTL identified. Assessing adaptation to heat stress conditions as the combination of performance and responsiveness offers breeders opportunities to select for grain yield stability across a range of environments, as well as genotypes with higher relative yield in stress conditions.
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