Executive dysfunction occurs in sickle cell anemia, but there are few early data. Infants
with sickle cell anemia (n = 14) and controls (n = 14) performed the “A-not-B” and Object
Retrieval search ...tasks, measuring precursors of executive function at 9 and 12 months.
Significant group differences were not found. However, for the A-not-B task, 7 of 11
sickle cell anemia infants scored in the lower 2 performance categories at 9 months, but
only 1 at 12 months (P = .024); controls obtained scores at 12 months
that were statistically comparable to the scores they had already obtained at 9 months. On
the Object Retrieval task, 9- and 12-month controls showed comparable scores, whereas
infants with sickle cell anemia continued to improve (P = .027); at 9
months, those with lower hemoglobin oxygen saturation passed fewer trials
(R
s = 0.670, P = .024) and took longer to obtain the toy
(R
s = –0.664, P = .013). Subtle delays in acquiring
developmental skills may underlie abnormal executive function in childhood.
The pathophysiology, clinical presentation, and natural history of acute pain in sickle cell disease are unique and require a disease-centered approach that also applies general principles of acute ...and chronic pain management. The majority of acute pain episodes are managed at home without the need to access health care. The long-term consequences of poorly treated acute pain include chronic pain, adverse effects of chronic opioid usage, psychological maladjustment, poor quality of life, and excessive health care utilization. There is no standard protocol for management of an acute pain crisis in either the hospital or the community. The assumptions that severe acute pain must be managed in the hospital with parenteral opioids and that strong opioids are needed for home management of pain need to be questioned. Pain management in the emergency department often does not meet acceptable standards, while chronic use of strong opioids is likely to result in opioid-induced hyperalgesia, exacerbation of chronic pain symptoms, and opioid dependency. We suggest that an integrated approach is needed to control the underlying condition, modify psychological responses, optimize social support, and ensure that health care services provide safe, effective, and prompt treatment of acute pain and appropriate management of chronic pain. This integrated approach should begin at an early age and continue through the adolescent, transition, and adult phases of the care model.
For many patients with sickle cell disease (SCD), jaundice is a significant clinical disease manifestation that impacts on patient well-being. We report a case of a patient with SCD and chronic ...jaundice treated with voxelotor (GBT440), a novel small molecule hemoglobin oxygen affinity modulator and potential disease-modifying therapy for SCD. The case patient is a 27-year-old Black male with a long history of SCD with clinical jaundice and scleral icterus. After starting voxelotor, the patient reported that his jaundice cleared within one week, and that he felt much better with more energy, and was relieved after his eyes cleared. Voxelotor reduced bilirubin and unconjugated bilirubin (by up to 76%), and hemoglobin improved from 9.9 g/dL at baseline to 11.1 g/dL at 90 days. Jaundice impacts many adults with SCD, significantly impacting self-image. Voxelotor treatment reduced bilirubin levels and improved jaundice, resulting in an improved sense of well-being in our case patient.
Objectives
We evaluated routine healthcare management, clinical status and patient‐ and carer‐reported outcomes in UK paediatric and adult patients with transfusion‐dependent β‐thalassaemia (TDT).
...Methods
A multi‐centre, observational mixed‐methodology study evaluated 165 patients (50% male; median age 24.1 interquartile range (IQR) 11.8–37.2 years) from nine UK centres.
Results
Patients had a mean of 13.7 (standard deviation SD ±3.2) transfusion episodes/year (mean retrospective observation period 4.7 ±0.7 years). The median (IQR) for iron overload parameters at the last assessment during the observation period were: serum ferritin (n = 165) 1961.0 (1090.0–3003.0) μg/L (38% > 2500 μg/L); R2 liver iron (n = 119) 5.4 (2.9–11.6) mg/g (16% ≥15 mg/g); T2* cardiac iron (n = 132) 30.3 (22.0–37.1) ms (10% < 10 ms). All patients received ≥1 iron chelator during the observation period; 21% received combination therapy. Patients had a mean of 7.8 (±8.1) non‐transfusion‐related hospital attendances or admissions/year. Adult patients’ mean EQ‐5D utility score was 0.69 (±0.33; n = 94 ≥16 years) and mean Transfusion‐dependent quality of life score was 58.6 (±18.4; n = 94 ≥18 years). For Work Productivity and Activity impairment, mean activity impairment for patients ≥18 years (n = 88) was 48% (±32%) and for carers (n = 29) was 28% (±23%).
Conclusions
TDT presents significant burden on patients, carers and healthcare resources.
Abstract Sickle Cell Disease (SCD) is the commonest inherited disorder in England, affecting 1 in 2000 births, the majority born in London and of Black African family origins. Newborn bloodspot ...screening for SCD has now been implemented across the whole of England and this review considers the neonatal screening pathway and aspects of out-patient and community care which should be delivered within the comprehensive care networks. Morbidity and mortality during childhood has declined due to implementation of effective care programmes which include infection and stroke prophylaxis. Children still suffer from complications of SCD affecting long-term health, quality of life, self esteem, school performance, and attainment. Treatment options for long-term control of the disease include hydroxycarbamide, regular transfusion and sibling allogeneic bone marrow transplantation. The indications, evidence of efficacy, and adverse effects of these treatments are discussed.
Background Sickle Cell Disease (SCD) is a genetic disorder caused by an HBB gene mutation and resulting structural variant haemoglobin (HbS) that polymerises upon deoxygenation, leading to a sickled ...morphology of red blood cells ( Chakravorty et al., Arch Dis Child 2015). This causes acute pain episodes, known as vaso-occlusive crises (VOC), that can result in severe end-organ damage in the long-term and a shortened lifespan ( Jang et al., J Transl Med 2021). Responsible for an estimated 95% of SCD hospitalisations and as a key predictor of death ( Darbari et al., Eur J Haematol 2020, Ballas et al., Am J Hematol 2005), it is critical to find new ways to drive early detection of VOCs in order to support preventative interventions. Aims This work aimed to develop a machine learning (ML) algorithm capable of predicting the potential onset of a VOC, using physiological data captured longitudinally by a wearable smartwatch, as well as patient-reported outcomes (PROs) entered via a specialised mobile phone application. Methods Following informed patient consent, participants gained access to a mobile phone application, or “digital patient wallet”, encompassing their health data and access to a PRO entry portal ( Summers et al., HemaSphere 2023). This allowed for daily recording of PROs including EQ-5D-5L, pain, mood, and fatigue scores, alongside self-reported VOCs. Participants were also provided with a Withings ScanWatch to be worn day and night, capturing physical activity, sleep quality, and heart rate data in an automated manner. Medical record data including healthcare utilisation, pathology, and demographic data was obtained through participant completion of a Subject Access Request form. Data for a snapshot cohort of 186 patients over a 1-month period (May-June 2023) were analysed through an ensemble of ML models: gradient boosting machine, neural network, and k-means clustering. All collated metrics were fed into the model, with the exclusion of hospitalisation as an 'a posteriori' variable, to ensure predictions were based on appropriate variables and not strengthened by self-confirming factors. The resulting predicted likelihood of a VOC for each participant was calculated on each day and given as a scale from 0-100%, with a likelihood of 75% or higher deemed to be a predicted VOC. This was then assessed against the true incidence of the participants' self-reported VOCs. Results The mean age was 36 (SD 11.6) years, and most patients were female (70%). The HbSS genotype was most common (75%), followed by HbSC (16%), and HbS Beta + Thalassemia (5%). 82,804 datapoints were collated for all participants across this period, encompassing 90 different variables. 69 instances of a VOC were self-reported by patients during the period of analysis, 58 (84%) of which were accurately predicted by the algorithm. 2,366 instances of no VOC were self-recorded, giving a negative predicted value of 83% (1,958/2,366 predicted). Further breakdown by the predicted likelihood score is displayed in Figure 2, highlighting the spread of individually calculated VOC likelihood scores per day against the incidence of patient-reported VOCs. Summary/Conclusions This work provides an important translation of daily trackable metrics through a remote, digital ecosystem, to the real-world prediction of potential VOC events in SCD. The purpose of this algorithm is, at its core, to act as a pre-emptive warning system from which proactive behavioural changes or interventions can be enacted. As such, the prediction of additional potential risk scores above the 75% threshold reflects an approach of ‘over-predicting’ considered to be a preferable strategy for the algorithm, given the severe nature of VOCs and the health impacts of missing a potential event. Our ongoing aim is to further develop the algorithm and its contributing metrics against medical data, in addition to patient self-reported events, to further optimise the predictor. This includes the curation of core metrics requiring minimal patient input, in order to reduce missing datapoints across those that feed into the algorithm and thereby reduce unpredicted VOCs. Ultimately, we hope to provide an early alert system that will help patients to identify their VOCs sooner, and thus action the next steps that may prevent possible hospital admissions.
Abstract 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 understand warning symptoms and signs which obligate assessment in hospital. It is also important that the parents have a good awareness of the symptoms and when and how to seek help. The common complications which may be encountered in an acute hospital setting are described together with recommendations for their management based on published evidence and the author’s experience.
Each of the pathogenic human retroviruses (HIV-1/2 and HTLV-1) has a nonhuman primate counterpart, and the presence of these retroviruses in humans results from interspecies transmission. The passage ...of another simian retrovirus, simian foamy virus (SFV), from apes or monkeys to humans has been reported. Mandrillus sphinx, a monkey species living in central Africa, is naturally infected with SFV. We evaluated the natural history of the virus in a free-ranging colony of mandrills and investigated possible transmission of mandrill SFV to humans.
We studied 84 semi-free-ranging captive mandrills at the Primate Centre of the Centre International de Recherches Médicales de Franceville (Gabon) and 15 wild mandrills caught in various areas of the country. The presence of SFV was also evaluated in 20 people who worked closely with mandrills and other nonhuman primates. SFV infection was determined by specific serological (Western blot) and molecular (nested PCR of the integrase region in the polymerase gene) assays. Seropositivity for SFV was found in 70/84 (83%) captive and 9/15 (60%) wild-caught mandrills and in 2/20 (10%) humans. The 425-bp SFV integrase fragment was detected in peripheral blood DNA from 53 captive and 8 wild-caught mandrills and in two personnel. Sequence and phylogenetic studies demonstrated the presence of two distinct strains of mandrill SFV, one clade including SFVs from mandrills living in the northern part of Gabon and the second consisting of SFV from animals living in the south. One man who had been bitten 10 years earlier by a mandrill and another bitten 22 years earlier by a macaque were found to be SFV infected, both at the Primate Centre. The second man had a sequence close to SFVmac sequences. Comparative sequence analysis of the virus from the first man and from the mandrill showed nearly identical sequences, indicating genetic stability of SFV over time.
Our results show a high prevalence of SFV infection in a semi-free-ranging colony of mandrills, with the presence of two different strains. We also showed transmission of SFV from a mandrill and a macaque to humans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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