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Journal of Pain and Symptom Management Jun 2024Outpatient palliative care (PC) has strong evidence demonstrating impact across serious illnesses, resulting in growing demand for skilled outpatient PC clinicians....
CONTEXT
Outpatient palliative care (PC) has strong evidence demonstrating impact across serious illnesses, resulting in growing demand for skilled outpatient PC clinicians. However, there is limited literature examining the existing state and quality of outpatient PC education during post-graduate training.
OBJECTIVES
Characterize the current state of outpatient training in United States (US) Hospice and Palliative Medicine (HPM) physician fellowships and elicit perceptions regarding quality of outpatient PC education.
METHODS
A cross-sectional survey of US adult HPM fellowship program directors (PDs) or their designee conducted between March-July 2023.
RESULTS
Of 161 programs, 85 participated (53% response rate) with representation across all US regions. HPM fellows spend a median of 4.8 weeks in outpatient PC compared to 24 weeks inpatient PC and 10.5 weeks in hospice settings. Over half (51%) of fellows saw outpatients from primarily one disease type with limited exposure to patients with other serious illnesses. Across programs, fellows' clinic structure, interdisciplinary team composition, and didactic experiences varied. On a 5-point rating scale, PDs reported significantly lower quality outpatient versus inpatient training (mean rating: 3.58 vs. 4.62, p< 0.001) and perceived fellows as less prepared for independent outpatient practice upon graduation (mean: 4.06 vs. 4.73, p< 0.001).
CONCLUSION
Our survey of US HPM fellowships identified multiple gaps between outpatient and inpatient PC education and training during fellowship and raises concern about the adequacy of outpatient PC training. To prepare the HPM workforce to meet the diverse needs of seriously ill populations and ensure adequate access, outpatient PC training requires reform.
PubMed: 38945458
DOI: 10.1016/j.jpainsymman.2024.06.017 -
The Journal of Pediatrics Jun 2024To describe reported adverse events (AEs) associated with elexacaftor/tezacaftor/ivacaftor (ETI) in a pediatric sample with cystic fibrosis (CF) aged 6-18 years, with at...
Reported Adverse Events in a Multicenter Cohort of Patients Ages 6-18 Years with Cystic Fibrosis and at Least one F508del Allele Receiving Elexacaftor/Tezacaftor/Ivacaftor.
OBJECTIVE
To describe reported adverse events (AEs) associated with elexacaftor/tezacaftor/ivacaftor (ETI) in a pediatric sample with cystic fibrosis (CF) aged 6-18 years, with at least one F508del variant, followed at multiple Italian CF centers.
STUDY DESIGN
This was a retrospective, multicenter, observational study. All children receiving ETI therapy from October 2019 to December 2023 were included. We assessed the prevalence and type of any reported potential drug-related AEs, regardless of discontinuation necessity. Persistent AEs were defined as those continuing at the end of the observation period.
RESULTS
Among 608 patients on ETI, 109 (17.9%) reported at least one AE. The majority (N=85, 77.9%) were temporary, with a median duration of 11 days (range 1-441 days). Only 7 (1.1%) patients permanently discontinued treatment, suggesting good overall safety of ETI. The most common AEs leading to discontinuation were transaminase elevations (temporary 14.1%, persistent 25.9%) and urticaria (temporary 41.2%, persistent 7.4%). Creatinine phosphokinase elevation was uncommon. No significant differences in AEs were observed based on sex, age groups (6-11 vs. 12-18 years), or genotype. Pre-existing CF-related liver disease was associated with an increased risk of transaminase elevations. We identified significant variability in the percentage of reported AEs (ANOVA p-value 0·026).
CONCLUSIONS
This real-world study highlights significant variability in reported AEs. Our findings suggest that ETI is a safe and well-tolerated therapy in children and adolescents with CF. However, further long-term safety and effectiveness investigations are warranted.
PubMed: 38945446
DOI: 10.1016/j.jpeds.2024.114176 -
The Journal of Pediatrics Jun 2024To demonstrate a high-yield molecular diagnostic workflow for lateralized overgrowth (LO), a congenital condition with abnormal enlargement of body parts, and to...
OBJECTIVE
To demonstrate a high-yield molecular diagnostic workflow for lateralized overgrowth (LO), a congenital condition with abnormal enlargement of body parts, and to classify it by molecular genetics. and STUDY DESIGN: We categorized 186 retrospective cases of LO diagnosed between 2003 and 2023 into suspected Beckwith-Wiedemann spectrum (BWSp), PIK3CA-Related Overgrowth Spectrum (PROS), vascular overgrowth (VO) , or isolated (ILO), based on initial clinical assessments, to determine the appropriate first-tier molecular tests and tissue for analysis. Patients underwent testing for 11p15 epigenetic abnormalities or somatic variants in genes related to PI3K/AKT/mTOR, vascular proliferation, and RAS-MAPK cascades using blood or skin DNA. For cases with negative initial tests, a sequential cascade molecular approach was employed to improve diagnostic yield.
RESULTS
This approach led to a molecular diagnosis in 54% of cases, 89% of cases consistent with initial clinical suspicions and 11% reclassified. BWSp was the most common cause, with 43% of cases exhibiting 11p15 abnormalities. PROS had the highest confirmation rate, with 74% of clinically diagnosed patients showing a PIK3CA variant. VO demonstrated significant clinical overlap with other syndromes. Molecular diagnosis of ILO proved challenging, with only 21% of cases classifiable into a specific condition.
CONCLUSION
Despite, LO is underdiagnosed from a molecular viewpoint and to date has had no diagnostic guidelines, which would be crucial for addressing potential cancer predisposition, enabling precision medicine treatments, or guiding management. This study sheds light on the molecular etiology of LO, highlighting the importance of tailored diagnostic approach and of selecting appropriate testing to achieve the highest diagnostic yield.
PubMed: 38945442
DOI: 10.1016/j.jpeds.2024.114177 -
Infection, Genetics and Evolution :... Jun 2024Chronic leg ulcers are hard to treat and can be a burden, particularly in resource-limited settings where diagnosis is a challenge. Staphylococcus aureus is among the...
BACKGROUND
Chronic leg ulcers are hard to treat and can be a burden, particularly in resource-limited settings where diagnosis is a challenge. Staphylococcus aureus is among the common bacteria isolated from chronic wounds with a great impact on wound healing, particularly in patients with co-morbidities. Antimicrobial resistance genes and virulence factors in Staphylococcus aureus isolates were assessed to support healthcare professionals to make better therapeutic choices, and importantly to curb the development and spread of antibiotic resistance.
METHODS
A cross-sectional study involved both inpatients and outpatients with chronic leg ulcers was conducted from August 2022 to April 2023 in 2 health facilities in Kilimanjaro region in Tanzania. Antimicrobial susceptibility testing was done using the disc diffusion method. Further, whole genome sequencing was performed to study the genotypic characteristics of the isolates.
RESULTS
A total of 92 participants were recruited in which 9 participants were only positive for 10 Staphylococcus aureus isolates upon culture. Five STs among 9 isolates were identified. Most of them belonged to ST8 (44%), with 1 isolate does not belong to any ST. Additionally, 50% of the isolates were methicillin-resistant Staphylococcus aureus (MRSA). All S. aureus isolates had almost similar virulence factors such as hemolysin, proteases and evasions that promote toxin production, protease production and host immune evasion respectively. Moreover, all mecA positive S. aureus isolates were phenotypically susceptible to cefoxitin.
CONCLUSION
Presence of mecA positive S. aureus isolates which are also phenotypically susceptible to cefoxitin implies the possibility of classifying MRSA as MSSA. This may result in the possible emergence of highly cefoxitin - resistant strains in health care and community settings when subsequently exposed to beta-lactam agents. Therefore, combination of whole genome sequencing and conventional methods is important in assessing bacterial resistance and virulence to improve management of patients.
PubMed: 38945421
DOI: 10.1016/j.meegid.2024.105631 -
Journal of Affective Disorders Jun 2024The association of a single time-point measure of sleep duration with cardio-metabolic disease has been extensively studied, but few studies have focused on the impact...
BACKGROUND
The association of a single time-point measure of sleep duration with cardio-metabolic disease has been extensively studied, but few studies have focused on the impact of sleep duration trajectory. This study aims to model the sleep duration trajectory as predictors for the subsequent development of cardio-metabolic disease.
METHODS
This study recruited a notably large population (n = 9883) of subjects aged at least 45 years from the China Health and Retirement Longitudinal Study (CHARLS), who participated in sequential surveys conducted in 2011, 2013, 2015, and 2018. Sleep duration trajectories were plotted using data of night sleep duration recorded at intervals from 2011 to 2015 by latent class trajectory model. The onset of cardio-metabolic diseases from 2015 to 2018 were confirmed and then the risk of different sleep duration trajectories on incident cardio-metabolic disease was examined using cox proportional hazards regression model.
RESULTS
We identified four sleep duration trajectories. Compared to the normal-stable trajectory, the short-stable trajectory was significantly associated with higher risk of incident stroke (hazard ratio [HR], 1.32; 95 % confidence interval [CI], 1.02 to 1.70), dyslipidemia (HR, 1.22; 95%CI, 1.01 to 1.49), and diabetes (HR, 1.42; 95%CI, 1.13 to 1.78) within three years of follow-up, and the short-increasing trajectory predicted a higher risk of incident stroke (HR, 2.38; 95%CI, 1.25 to 4.55).
CONCLUSIONS
Short sleep trajectory could increase the risk of incident stroke, dyslipidemia, and diabetes, and an increasing sleep trajectory was associated with increased risk of incident stroke among middle-aged and older Chinese adults.
PubMed: 38945401
DOI: 10.1016/j.jad.2024.06.114 -
The Journal of Pain Jun 2024Pain is an interpersonal and inherently social experience. Pain perception and administration of medical treatment all occur in a particular environmental and social... (Review)
Review
Pain is an interpersonal and inherently social experience. Pain perception and administration of medical treatment all occur in a particular environmental and social context. Early environmental influences, and early learning experiences and interactions, condition the body's response to different threats (like pain), ultimately shaping the underlying neurophysiology. These early interactions and experiences also determine what situations are perceived as threatening, as well as our belief in our own ability to self-manage, and our belief in others to offer support, during perceived threats. These beliefs intrinsically drive the combination of behaviours that emerge in response to perceived threats, including pain. Such behaviours can be categorised into attachment styles. In this interdisciplinary review, we synthesise and summarise evidence from the neurobiological, psychobiological, psychosocial and psychobehavioural fields, to describe how these beliefs are embedded in the brain's prediction models to generate a series of expectations/perceptions around the level of safety/threat in different contexts. As such, these beliefs may predict how one experiences, and responds to, pain; with potentially significant implications for the development and management of chronic pain. Little attention has been directed to the effect of adult attachment style on pain in research studies and in the clinical setting. Using interdisciplinary evidence, we argue why we think this interaction merits further consideration and research. PERSPECTIVE: This review explores the influence of attachment styles on pain perception, suggesting a link between social connections and chronic pain development. It aligns with recent calls to emphasise the social context in pain research and advocates for increased focus on adult attachment styles in research and clinical practice.
PubMed: 38945383
DOI: 10.1016/j.jpain.2024.104619 -
International Journal of Cardiology Jun 2024There is no universally followed protocol for managing Reflex Vasovagal syncope (VVS).
BACKGROUND
There is no universally followed protocol for managing Reflex Vasovagal syncope (VVS).
METHODS
VVS patients were treated with a 2 step protocol. Step I - counseling, hydration, physiotherapy, and Tadasana Yoga maneuver. Patients with ≥2 VVS recurrences were given step II care - intensification of step I, elastic stockings,and pharmacotherapy. Follow-up included assessment by periodic functional status questionnaires.
RESULTS
157 patients (103 males & 54 females,mean age - 53 ± 20 years & mean LVEF - 62 ± 5%.) experienced 837 total events - 382 syncopal, and 485 near syncopal episodes over 14 ± 9 months. After step I protocol, the mean total, syncopal and near syncopal events declined from 5 ± 7 to 0.3 ± 1.2 (P < 0.0001), 3 ± 2 to 0.1 ± 0.4 (P < 0.0001) and 3 ± 6 to 0.2 ± 1.1 (P < 0.0001) respectively . Twenty (12.7%) patients had 53 event recurrences, 15- syncopal episodes in 7 and 38 near syncope events in 13. After step II, 5 patients had 14 events. At 33 ± 15 months, in 152 patients (96.8%) there were no recurrences and syncope was prevented in all (100%). The median total, syncopal and near syncopal events declined from 3 to 0,(p < 0.001) 2 to 0 (p < 0.001) and 1 to 0 (p < 0.001) respectively. There was an improvement in all the 3 quality of life parameters.
CONCLUSION
We demonstrate a simple and effective protocol that can be universally adopted to prevent VVS recurrences,with improvement in quality of life.
PubMed: 38945370
DOI: 10.1016/j.ijcard.2024.132302 -
Chest Jun 2024Childhood asthma is a prevalent condition with potential impact on adult life.
BACKGROUND
Childhood asthma is a prevalent condition with potential impact on adult life.
RESEARCH QUESTION
In a 60-year follow-up study of adults with a history of severe childhood asthma, what are the potential differences in characteristics between individuals with persistent asthma and asthma remission in adulthood?
STUDY DESIGN AND METHODS
Danish adults with a history of childhood asthma and a 4-month stay in at an asthma care facility in Kongsberg, Norway (1950-1979) in childhood were included. Recruitment was done through social media and personal invitation letters. Participants completed questionnaires and underwent spirometry, bronchial provocation, and bronchodilator reversibility and blood tests. Asthma remission was defined as no use of asthma medication and no asthma symptoms within the past 12 months with the remaining participants being classified as having current asthma.
RESULTS
Among 1394 eligible participants, 232 completed the follow-up. Ninety percent had current asthma, of whom 26% reported exacerbations in the past year. Only 16% of all the participants were managed in secondary care. Common comorbidities were allergic rhinitis (60%), hypertension (21%), eczema (16%), and cataract (8%). Compared to participants in remission, participants with persistent asthma had higher total immunoglobulin E (p=0.03), and both lower FEV%pred (p=0.03), and FEV/FVC ratio (p<0.001), as well as numerically higher fractional exhaled nitric oxide and blood eosinophil count.
INTERPRETATION
Our 60-year follow-up study of adults with a history of severe childhood asthma revealed that nine out of ten still had current asthma. Persistent asthma was associated with lower lung function and higher levels of type 2 inflammatory biomarkers compared to those with asthma remission.
PubMed: 38945358
DOI: 10.1016/j.chest.2024.06.005 -
Chest Jun 2024
PubMed: 38945357
DOI: 10.1016/j.chest.2024.06.009 -
Journal of Controlled Release :... Jun 2024Vascular diseases constitute a significant contributor to worldwide mortality rates, placing a substantial strain on healthcare systems and socio-economic aspects. They... (Review)
Review
Vascular diseases constitute a significant contributor to worldwide mortality rates, placing a substantial strain on healthcare systems and socio-economic aspects. They are closely associated with inflammatory responses, as sustained inflammation could impact endothelial function, the release of inflammatory mediators, and platelet activation, thus accelerating the progression of vascular diseases. Consequently, directing therapeutic efforts towards mitigating inflammation represents a crucial approach in the management of vascular diseases. Traditional anti-inflammatory medications may have extensive effects on multiple tissues and organs when absorbed through the bloodstream. Conversely, treatments targeting inflammatory vascular diseases, such as monoclonal antibodies, drug-eluting stents, and nano-drugs, can achieve more precise effects, including precise intervention, minimal non-specific effects, and prolonged efficacy. In addition, personalized therapy is an important development trend in targeted therapy for inflammatory vascular diseases. Leveraging advanced simulation algorithms and clinical trial data, treatment strategies are gradually being personalized based on patients' genetic, biomarker, and clinical profiles. It is expected that the application of precision medicine in the field of vascular diseases will have a broader future. In conclusion, targeting therapies offer enhanced safety and efficacy compared to conventional medications; investigating novel targeting therapies and promoting clinical transformation may be a promising direction in improving the prognosis of patients with inflammatory vascular diseases. This article reviews the pathogenesis of inflammatory vascular diseases and presents a comprehensive overview of the potential for targeted therapies in managing this condition.
PubMed: 38945301
DOI: 10.1016/j.jconrel.2024.06.063