Analysis of Reports on Adverse Drug Reactions Related to Herbal Medicinal Products and Herbal Supplements in the Netherlands Received by the National Pharmacovigilance Centre Lareb

Drug Saf. 2022 May 24. doi: 10.1007/s40264-022-01180-5. Online ahead of print.

ABSTRACT

INTRODUCTION: The inclusion of herbal medicinal products and herbal supplements in pharmacovigilance systems is important because a systematic approach of collecting and analyzing adverse drug reactions related to these products will help practitioners, patients, and regulators to gain more knowledge and prevent harm.

OBJECTIVE: We aimed to categorize the adverse drug reaction reports on herbal medicinal products and herbal supplements submitted to the Pharmacovigilance Centre Lareb between 1991 and February 2021 on the basis of their regulatory status, herbs included, and adverse drug reactions involved.

METHODS: We categorized products on the basis of their registration status and herbal ingredients. The products were then categorized according to the Herbal Anatomical Therapeutic Chemical Classification System. We used descriptive statistics in Microsoft Excel 2019. Pivot tables were used for the analysis and presentation of the data.

RESULTS: Until February 2021, a total of 789 reports of herbal medicinal products and herbal supplements were received by Lareb. In these reports, a total of 823 herbal products were labeled as suspect. These products caused a total of 1727 adverse drug reactions. Of the 823 products, 229 were registered as a medicine, and 594 were on the market as a herbal supplement. Of the 823 herbal products, 522 reports concerned single-herb products, 256 reports concerned combination products, 27 reports concerned vitamin products containing herbal ingredients, and 18 reports concerned product issues. Approximately 15% of reports concerned serious adverse drug reactions, and adulterated products harbored a high risk of causing serious adverse drug reactions.

CONCLUSIONS: Analysis of the herbal medicinal products and herbal supplements in the Dutch pharmacovigilance database revealed a variety of suspected herbal ingredients. The reports provide insight into the variety of herbal products used in the Netherlands and the adverse reactions associated with their use. Pharmacovigilance of herbal products is essential to ensure their safe use.

PMID:35608783 | DOI:10.1007/s40264-022-01180-5

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Clinicopathological Features, MCPyV Status and Outcomes of Merkel Cell Carcinoma in Solid-Organ Transplant Recipients: A Retrospective, Multicenter Cohort Study

J Eur Acad Dermatol Venereol. 2022 May 24. doi: 10.1111/jdv.18256. Online ahead of print.

ABSTRACT

BACKGROUND: The proportion of Merkel cell carcinomas (MCCs) in solid-organ transplant recipients (SOTR) harboring Merkel cell polyomavirus (MCPyV) is unknown, as are factors affecting their outcomes.

OBJECTIVE: To describe clinicopathologic features of MCC in SOTR, investigate the tumoral MCPyV-status and identify factors associated with tumor outcomes.

METHODS: Retrospective, international, cohort-study. MCPyV-status was investigated by immunohistochemistry and polymerase chain reaction.

RESULTS: Thirty SOTR and 44 consecutive immunocompetent patients with MCC were enrolled. SOTR were younger at diagnosis (69 vs 78 years, p<.001). Thirty-three percent of SOTR MCCs were MCPyV-positive vs 91% of immunocompetent MCCs (p=.001). Solid-organ transplantation was associated with an increased cumulative incidence of progression (SHR: 3.35 [1.57-7.14], p=.002), MCC-specific mortality (SHR: 2.55 [1.07-6.06], p=.034) and overall mortality (HR: 3.26 [1.54-6.9], p=.002). MCPyV-positivity and switching to an mTOR inhibitor (mTORi) after MCC diagnosis were associated with an increased incidence of progression (SHR: 4.3 [1.5-13], p=.008 and SHR: 3.6 [1.1-12], p=.032, respectively) in SOTR.

LIMITATIONS: Retrospective design and heterogeneity of SOTR cohort.

CONCLUSIONS: MCPyV appears to play a less prominent role in the etiopathogenesis of MCC in SOTR. SOTR have a worse prognosis than their immunocompetent counterparts and switching to an mTORi after the diagnosis of MCC does not improve progression.

PMID:35607918 | DOI:10.1111/jdv.18256

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Sustained complete response of metastatic cutaneous squamous cell carcinoma by immune checkpoint inhibition in a renal transplant patient: a case report

J Eur Acad Dermatol Venereol. 2022 May 24. doi: 10.1111/jdv.18262. Online ahead of print.

NO ABSTRACT

PMID:35607905 | DOI:10.1111/jdv.18262

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Best Practices to Implement Dried Blood Spot Sampling for Therapeutic Drug Monitoring in Clinical Practice

Ther Drug Monit. 2022 May 23. doi: 10.1097/FTD.0000000000000994. Online ahead of print.

ABSTRACT

BACKGROUND: Sampling of blood at home to determine the concentration of drugs or other compounds can be effective in limiting hospital-based sampling. This could lower hospital visits and patient burden, improve the quality of life, and reduce health care costs. Dried blood spot (DBS) microsampling is often used for this purpose, wherein, capillary blood, obtained by pricking the heel or finger, is used to measure different analytes. Although DBS has several advantages over venous blood sampling, it is not routinely implemented in clinical practice. To facilitate the bench to bedside transition, it is important to be aware of certain challenges that need to be considered and addressed.

RESULTS: Here, important considerations regarding the implementation of DBS in clinical practice, the choice of patients, blood sampling, transport, and laboratory analysis are discussed. In addition, we share our experience and provide suggestions on how to deal with these problems in a clinical setting.

PMID:35607881 | DOI:10.1097/FTD.0000000000000994

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What the snake leaves in its wake: Functional limitations and disabilities among snakebite victims in Ghanaian communities

PLoS Negl Trop Dis. 2022 May 23;16(5):e0010322. doi: 10.1371/journal.pntd.0010322. Online ahead of print.

ABSTRACT

BACKGROUND: The estimated five million snakebites per year are an important health problem that mainly affect rural poor populations. The global goal is to halve both mortality and morbidity from this neglected tropical disease by 2030. Data on snakebite morbidity are sparse and mainly obtained from hospital records.

METHODS: This community-based study was conducted among 379 rural residents with or without a history of snakebite in the Ashanti and Upper West regions of Ghana. All participants in the snakebite group were bitten at least six months before the day of survey. The World Health Organisation Disability Assessment Schedule 2.0 (WHODAS 2.0) and the Buruli Ulcer Functional Limitation Score were used to obtain patient-reported measure of functioning and disability. Long-term consequences were evaluated based on the severity of the symptoms at the time of the snakebite.

FINDINGS: The median (IQR) time since the snakebite was 8.0 (3.5-16.5) years. The relative risk of disability was 1.54 (95% CI, 1.17-2.03) in the snakebite group compared to the community controls. Among patients with clinical symptoms suggesting envenoming at the time of bite, 35% had mild/moderate disabilities compared to 20% in the control group. The disability domains mainly affected by snakebite envenoming were cognition level, mobility, life activities and participation in society. A combination of the severity of symptoms at the time of the bite, age, gender and region of residence most accurately predicted the odds of having functional limitations and disabilities.

CONCLUSION: The burden of snakebite in the community includes long-term disabilities of mild to moderate severity, which need to be considered when designing appropriate public health interventions. Estimating the total burden of snakebite is complicated by geographic differences in types of snakes and their clinical manifestations.

PMID:35604939 | DOI:10.1371/journal.pntd.0010322

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Prevalence of scoliosis and impaired pulmonary function in patients with type III osteogenesis imperfecta

Eur Spine J. 2022 May 23. doi: 10.1007/s00586-022-07260-5. Online ahead of print.

ABSTRACT

PURPOSE: Osteogenesis Imperfecta (OI) is a rare group of congenital genetic disorders that consists of a collagen synthesis defect. The most severe phenotype is type III OI. Characterized by progressive bone deformity, fragility and pulmonary impairment, causing significant morbidity and mortality. Also, multilevel spine deformities are observed, such as scoliosis. The literature on the pathophysiology of pulmonary impairment in relation to scoliosis in these patients is scarce and conflicting. This study aims to determine the prevalence of scoliosis and its relation to pulmonary function in type III OI patients.

METHODS: This retrospective cohort study took place between April 2020 and November 2021. Forty-two patients with type III OI were included. Anterior-posterior spine radiographs were evaluated for scoliosis. Pulmonary function was assessed using spirometry and partial pressure of carbon dioxide.

RESULTS: All 42 patients had scoliosis, with a mean curve of 66° (95% CI of range). Vital lung capacity was decreased, compared to a non-OI population (mean 1.57 L). This was correlated to the degree of scoliosis (st. β – 0.40, P = 0.03), especially in increasing thoracic curves. Restrictive lung pathophysiology was shown in our study population with a mean FEV1/FVC ratio of 0.85.

CONCLUSIONS: Increasing thoracic scoliosis was correlated with decreased vital lung capacity in our study population of type III OI patients. High FEV1/FVC ratios found in this study population show restrictive lung pathophysiology. Therefore, it is plausible that the pulmonary impairment found in type III OI patients is a combined issue, partly associated to scoliosis and partly intrinsic to OI.

PMID:35604455 | DOI:10.1007/s00586-022-07260-5

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Autologous Skin Fibroblast-Based PLGA Nanoparticles for Treating Multiorgan Fibrosis

Adv Sci (Weinh). 2022 May 23:e2200856. doi: 10.1002/advs.202200856. Online ahead of print.

ABSTRACT

Fibrotic diseases remain a substantial health burden with few therapeutic approaches. A hallmark of fibrosis is the aberrant activation and accumulation of myofibroblasts, which is caused by excessive profibrotic cytokines. Conventional anticytokine therapies fail to undergo clinical trials, as simply blocking a single or several antifibrotic cytokines cannot abrogate the profibrotic microenvironment. Here, biomimetic nanoparticles based on autologous skin fibroblasts are customized as decoys to neutralize multiple fibroblast-targeted cytokines. By fusing the skin fibroblast membrane onto poly(lactic-co-glycolic) acid cores, these nanoparticles, termed fibroblast membrane-camouflaged nanoparticles (FNPs), are shown to effectively scavenge various profibrotic cytokines, including transforming growth factor-β, interleukin (IL)-11, IL-13, and IL-17, thereby modulating the profibrotic microenvironment. FNPs are sequentially prepared into multiple formulations for different administration routines. As a proof-of-concept, in three independent animal models with various organ fibrosis (lung fibrosis, liver fibrosis, and heart fibrosis), FNPs effectively reduce the accumulation of myofibroblasts, and the formation of fibrotic tissue, concomitantly restoring organ function and indicating that FNPs are a potential broad-spectrum therapy for fibrosis management.

PMID:35603964 | DOI:10.1002/advs.202200856

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The Exponentially Weighted Moving Average Procedure for Detecting Changes in Intensive Longitudinal Data in Psychological Research in Real-Time: A Tutorial Showcasing Potential Applications

Assessment. 2022 May 22:10731911221086985. doi: 10.1177/10731911221086985. Online ahead of print.

ABSTRACT

Affect, behavior, and severity of psychopathological symptoms do not remain static throughout the life of an individual, but rather they change over time. Since the rise of the smartphone, longitudinal data can be obtained at higher frequencies than ever before, providing new opportunities for investigating these person-specific changes in real-time. Since 2019, researchers have started using the exponentially weighted moving average (EWMA) procedure, as a statistically sound method to reach this goal. Real-time, person-specific change detection could allow (a) researchers to adapt assessment intensity and strategy when a change occurs to obtain the most useful data at the most useful time and (b) clinicians to provide care to patients during periods in which this is most needed. The current paper provides a tutorial on how to use the EWMA procedure in psychology, as well as demonstrates its added value in a range of potential applications.

PMID:35603660 | DOI:10.1177/10731911221086985

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Don’t Miss the Moment: A Systematic Review of Ecological Momentary Assessment in Suicide Research

Front Digit Health. 2022 May 6;4:876595. doi: 10.3389/fdgth.2022.876595. eCollection 2022.

ABSTRACT

Suicide and suicide-related behaviors are prevalent yet notoriously difficult to predict. Specifically, short-term predictors and correlates of suicide risk remain largely unknown. Ecological momentary assessment (EMA) may be used to assess how suicidal thoughts and behaviors (STBs) unfold in real-world contexts. We conducted a systematic literature review of EMA studies in suicide research to assess (1) how EMA has been utilized in the study of STBs (i.e., methodology, findings), and (2) the feasibility, validity and safety of EMA in the study of STBs. We identified 45 articles, detailing 23 studies. Studies mainly focused on examining how known longitudinal predictors of suicidal ideation perform within shorter (hourly, daily) time frames. Recent studies have explored the prospects of digital phenotyping of individuals with suicidal ideation. The results indicate that suicidal ideation fluctuates substantially over time (hours, days), and that individuals with higher mean ideation also have more fluctuations. Higher suicidal ideation instability may represent a phenotypic indicator for increased suicide risk. Few studies succeeded in establishing prospective predictors of suicidal ideation beyond prior ideation itself. Some studies show negative affect, hopelessness and burdensomeness to predict increased ideation within-day, and sleep characteristics to impact next-day ideation. The feasibility of EMA is encouraging: agreement to participate in EMA research was moderate to high (median = 77%), and compliance rates similar to those in other clinical samples (median response rate = 70%). More individuals reported suicidal ideation through EMA than traditional (retrospective) self-report measures. Regarding safety, no evidence was found of systematic reactivity of mood or suicidal ideation to repeated assessments of STBs. In conclusion, suicidal ideation can fluctuate substantially over short periods of time, and EMA is a suitable method for capturing these fluctuations. Some specific predictors of subsequent ideation have been identified, but these findings warrant further replication. While repeated EMA assessments do not appear to result in systematic reactivity in STBs, participant burden and safety remains a consideration when studying high-risk populations. Considerations for designing and reporting on EMA studies in suicide research are discussed.

PMID:35601888 | PMC:PMC9120419 | DOI:10.3389/fdgth.2022.876595

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Proton therapy of a pregnant patient with nasopharyngeal carcinoma

Clin Transl Radiat Oncol. 2022 May 4;35:33-36. doi: 10.1016/j.ctro.2022.04.014. eCollection 2022 Jul.

ABSTRACT

BACKGROUND AND PURPOSE: Radiotherapy during pregnancy is rarely administered due to lack of data and practical challenges. This is the first detailed report of proton therapy as cancer treatment for a pregnant patient with nasopharyngeal carcinoma.

MATERIALS AND METHODS: Pencil beam scanning proton therapy was prescribed to a pregnant patient to a total dose of 70 Gy (RBE) to the therapeutic CTV and 54.25 Gy to the prophylactic CTV, delivered in 35 fractions with a simultaneous integrated boost technique.

RESULTS: Phantom measurements showed a thirty-fold decrease in fetal radiation dose when using proton compared to photon therapy, with a total fetal dose of 5.5 mSv for the complete proton treatment, compared to 185 and 298 mSv for the photon treatment with and without lead shielding, respectively. After adminstering proton therapy during pregnancy, at 39 weeks of gestation, a healthy boy with a birthweight on the 83th percentile was delivered. Pediatric follow-up at 2 months of age of the offspring showed normal growth and age-adequate motor development with no signs of neurological problems. MR follow-up of the tumor 3 months after the end of treatment showed complete remission.

CONCLUSION: This case demonstrates the potential of proton therapy for treatment during pregnancy.Compared to photon therapy, proton therapy can significantly limit fetal dose, while simultaneously offering a more optimized treatment to the patient.

PMID:35601798 | PMC:PMC9114153 | DOI:10.1016/j.ctro.2022.04.014

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Telomere length declines with age, but relates to immune function independent of age in a wild passerine

R Soc Open Sci. 2022 Apr 27;9(4):212012. doi: 10.1098/rsos.212012. eCollection 2022 Apr.

ABSTRACT

Telomere length (TL) shortens with age but telomere dynamics can relate to fitness components independent of age. Immune function often relates to such fitness components and can also interact with telomeres. Studying the link between TL and immune function may therefore help us understand telomere-fitness associations. We assessed the relationships between erythrocyte TL and four immune indices (haptoglobin, natural antibodies (NAbs), complement activity (CA) and heterophil-lymphocyte (HL) ratio; n = 477-589), from known-aged individuals of a wild passerine (Malurus coronatus). As expected, we find that TL significantly declined with age. To verify whether associations between TL and immune function were independent of parallel age-related changes (e.g. immunosenescence), we statistically controlled for sampling age and used within-subject centring of TL to separate relationships within or between individuals. We found that TL positively predicted CA at the between-individual level (individuals with longer average TL had higher CA), but no other immune indices. By contrast, age predicted the levels of NAbs and HL ratio, allowing inference that respective associations between TL and age with immune indices are independent. Any links existing between TL and fitness are therefore unlikely to be strongly mediated by innate immune function, while TL and immune indices appear independent expressions of individual heterogeneity.

PMID:35601455 | PMC:PMC9043702 | DOI:10.1098/rsos.212012

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The effect of sarcopenic obesity and muscle quality on complications after DIEP-flap breast reconstruction

Heliyon. 2022 May 11;8(5):e09381. doi: 10.1016/j.heliyon.2022.e09381. eCollection 2022 May.

ABSTRACT

INTRODUCTION: The aim of this study was to evaluate whether sarcopenic obesity and muscle quality as expressed by skeletal muscle radiodensity (SMD) are associated to postoperative complications in women undergoing DIEP-flap breast reconstruction (BR).

METHODS: All patients who underwent DIEP-flap BR at our tertiary center between 2010 and 2018 were asked to sign informed consent for the use of their electronic medical records and images. By outlining anatomical skeletal muscle contours on the preoperative abdominal CT-scan at lumbar level L3, SMD and skeletal muscle indices (SMI) were measured by two observers independently. Using logistic regression analyses, the association between sarcopenic obesity (BMI >25 & SMI <39), low SMD (<40HU), and Clavien-Dindo (CD) grade ≥ II complications was evaluated. In this way odds ratios (OR) and adjusted odds ratios (ORadjusted) were provided.

RESULTS: Out of the 103 patients included in this study, 36% had CD grade ≥ II complications within 30 days of surgery. Twenty patients (19%) suffered from sarcopenic obesity of whom eleven patients (55%) had CD grade ≥ II complications (OR = 2.7, p = 0.05). In a multivariate analysis, sarcopenic obesity was not significantly related to a higher complication rate (ORadjusted = 2.2, p = 0.14) but women with SMD below average and those with prior radiotherapy had a higher risk for grade ≥ II complications (ORadjusted = 2.9, p = 0.02 and ORadjusted = 2.7, p = 0.02 respectively).

CONCLUSION: Below average SMD (<40HU) was found to be associated with the development of postoperative CD grade ≥ II complications in women undergoing DIEP-flap BR. Future research should evaluate whether improving SMD reduces the complication incidence in this patient group.

PMID:35600454 | PMC:PMC9118656 | DOI:10.1016/j.heliyon.2022.e09381

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Inherited thrombophilia transpires with severe coronary arterial thrombosis in wide range of age backgrounds: A report of 3 cases

Ann Med Surg (Lond). 2022 May 10;78:103730. doi: 10.1016/j.amsu.2022.103730. eCollection 2022 Jun.

ABSTRACT

INTRODUCTION: and importance: Protein C and S deficiency are some of the coagulation cascade disorders which may also contributes not only to venous thromboembolism (VTE), but also rarely to arterial thrombosis. Here we present a report of 3 severe coronary artery disease (CAD) cases ranging from very young to elderly patients with concomitant inherited thrombophilia.

CASE PRESENTATION: The first case was a chronic coronary syndrome from a very young male patient with history of VTE without any other risk factor of CAD. The second case was about premature CAD with triple chronic total occlusion (RCA, LCX, LAD) in patient under 45 years old, with single risk factor. The third case was about accelerated atherosclerosis progression from previously non significant stenosis in RCA into total occlusion in RCA and inferior STEMI in old patient on supposely adequate double anti platelet agent.

CLINICAL DISCUSSION: All patients had protein C and/or S deficiency and first degree family history of VTE, therefore inherited thrombophilia was diagnosed. We gave them oral anticoagulant in addition to their standard treatment for secondary prevention with good outcome and without further adverse event.

CONCLUSION: It is important to raise awareness to perform screening inherited thrombophilia as an important risk factor for CAD in special subgroup such as young age patient with rapid course progression and family history of VTE. The use of oral anticoagulants as either prophylactic or therapeutic purpose in patients with inherited thrombophilia are safe and effective. However, further research is still needed.

PMID:35600193 | PMC:PMC9118514 | DOI:10.1016/j.amsu.2022.103730

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Low Cancer Incidence in Naked Mole-Rats May Be Related to Their Inability to Express the Warburg Effect

Front Physiol. 2022 May 4;13:859820. doi: 10.3389/fphys.2022.859820. eCollection 2022.

ABSTRACT

Metabolic flexibility in mammals enables stressed tissues to generate additional ATP by converting large amounts of glucose into lactic acid; however, this process can cause transient local or systemic acidosis. Certain mammals are adapted to extreme environments and are capable of enhanced metabolic flexibility as a specialized adaptation to challenging habitat niches. For example, naked mole-rats (NMRs) are a fossorial and hypoxia-tolerant mammal whose metabolic responses to environmental stressors markedly differ from most other mammals. When exposed to hypoxia, NMRs exhibit robust hypometabolism but develop minimal acidosis. Furthermore, and despite a very long lifespan relative to other rodents, NMRs have a remarkably low cancer incidence. Most advanced cancers in mammals display increased production of lactic acid from glucose, irrespective of oxygen availability. This hallmark of cancer is known as the Warburg effect (WE). Most malignancies acquire this metabolic phenotype during their somatic evolution, as the WE benefits tumor growth in several ways. We propose that the peculiar metabolism of the NMR makes development of the WE inherently difficult, which might contribute to the extraordinarily low cancer rate in NMRs. Such an adaptation of NMRs to their subterranean environment may have been facilitated by modified biochemical responses with a stronger inhibition of the production of CO2 and lactic acid by a decreased extracellular pH. Since this pH-inhibition could be deeply hard-wired in their metabolic make-up, it may be difficult for malignant cells in NMRs to acquire the WE-phenotype that facilitates cancer growth in other mammals. In the present commentary, we discuss this idea and propose experimental tests of our hypothesis.

PMID:35600297 | PMC:PMC9114474 | DOI:10.3389/fphys.2022.859820

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How Physicians Discuss Uncertainty With Parents in Intensive Care Units

Pediatrics. 2022 May 23:e2021055980. doi: 10.1542/peds.2021-055980. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Physicians and parents of critically ill neonates and children receiving intensive care have to make decisions on the child’s behalf. Throughout the child’s illness and treatment trajectory, adequately discussing uncertainties with parents is pivotal because this enhances the quality of the decision-making process and may positively affect the child’s and parents’ well-being. We investigated how physicians discuss uncertainty with parents and how this discussion evolves over time during the trajectory.

METHODS: We asked physicians working in the NICU and PICU of 3 university medical centers to audio record their conversations with parents of critically ill children from the moment doubts arose whether treatment was in the child’s best interests. We qualitatively coded and analyzed the anonymized transcripts, thereby using the software tool MAXQDA 2020.

RESULTS: Physicians were found to adapt the way they discussed uncertainty with parents to the specific phase of the child’s illness and treatment trajectory. When treatment options were still available, physicians primarily focused on uncertainty related to diagnostic procedures, treatment options, and associated risks and effects. Particularly when the child’s death was imminent, physicians had less “scientific” guidance to offer. They eliminated most uncertainty and primarily addressed practical uncertainties regarding the child’s dying process to offer parents guidance.

CONCLUSIONS: Our insights may increase physicians’ awareness and enhance their skills in discussing uncertainties with parents tailored to the phase of the child’s illness and treatment trajectory and to parental needs in each specific phase.

PMID:35603505 | DOI:10.1542/peds.2021-055980

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Sex differences in efficacy of pharmacological therapies in heart failure with reduced ejection fraction: a meta-analysis

ESC Heart Fail. 2022 May 23. doi: 10.1002/ehf2.13974. Online ahead of print.

ABSTRACT

AIMS: Recent studies have suggested potential sex differences in treatment response to pharmacological therapies in heart failure (HF). We performed a systematic review and meta-analysis of studies comparing treatment effects between men and women with HF and reduced ejection fraction (HFrEF) using established guideline-directed medical therapy and other emerging pharmacological treatments.

METHODS AND RESULTS: Systematic search was performed on PubMed, Embase, and Cochrane Library for randomized controlled trials published in 1990-2021. Outcomes were all-cause mortality and combined outcome of all-cause mortality and/or hospitalization for HF. Of 618 articles identified, 25 articles and 100 213 patients (mean age 62 ± 1.7 years, women 23.1%, mean left ventricular ejection fraction 26.6 ± 1.3%) were included in the systematic review and meta-analysis. For the outcome of all-cause mortality, there was no evidence of treatment heterogeneity by sex for renin-angiotensin system inhibitors (RASi) [hazard ratio (HR) 0.86 (95% confidence interval 0.75-0.99) in men; HR 0.97 (0.77-1.23) in women; Pinteraction = 0.288], or for beta-blockers (BB) [HR 0.71 (0.59-0.86) in men; HR 0.87 (0.73-1.03) in women; Pinteraction = 0.345]. Similarly, for the composite outcome of death or HF hospitalization, there was no evidence of treatment heterogeneity by sex for RASi [HR 0.84 (0.77-0.93) in men; HR 0.94 (0.81-1.08) in women; Pinteraction = 0.210] or BB [HR 0.76 (0.64-0.90) in men; HR 0.72 (0.60-0.86) in women; Pinteraction = 0.650]. Results for mineralocorticoid receptor antagonists (MRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) from previously published meta-analyses were included in the review. For the combined outcome of cardiovascular death or HF hospitalization, no significant interaction for sex was observed for MRA (Pinteraction = 0.78) or SGLT2i (Pinteraction = 0.37). Results for emerging pharmacological treatments, such as soluble guanylate cyclase stimulators and cardiac myosin activators, were included in the review and showed consistent treatment effects between men and women.

CONCLUSIONS: Our meta-analysis showed no differences between sex in treatment effect for BB and RASi. Review on previously published trials for MRA, SGLT2i, and emerging therapies presented consistent treatment effects between men and women.

PMID:35603531 | DOI:10.1002/ehf2.13974

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Clean and Safe Drinking Water Systems <em>via</em> Metagenomics Data and Artificial Intelligence: State-of-the-Art and Future Perspective

Front Microbiol. 2022 May 5;13:832452. doi: 10.3389/fmicb.2022.832452. eCollection 2022.

ABSTRACT

The use of next-generation sequencing technologies in drinking water distribution systems (DWDS) has shed insight into the microbial communities’ composition, and interaction in the drinking water microbiome. For the past two decades, various studies have been conducted in which metagenomics data have been collected over extended periods and analyzed spatially and temporally to understand the dynamics of microbial communities in DWDS. In this literature review, we outline the findings which were reported in the literature on what kind of occupancy-abundance patterns are exhibited in the drinking water microbiome, how the drinking water microbiome dynamically evolves spatially and temporally in the distribution networks, how different microbial communities co-exist, and what kind of clusters exist in the drinking water ecosystem. While data analysis in the current literature concerns mainly with confirmatory and exploratory questions pertaining to the use of metagenomics data for the analysis of DWDS microbiome, we present also future perspectives and the potential role of artificial intelligence (AI) and mechanistic models to address the predictive and mechanistic questions. The integration of meta-omics, AI, and mechanistic models transcends metagenomics into functional metagenomics, enabling deterministic understanding and control of DWDS for clean and safe drinking water systems of the future.

PMID:35602066 | PMC:PMC9121918 | DOI:10.3389/fmicb.2022.832452

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Development and multicenter validation of chest X-ray radiography interpretations based on natural language processing

Commun Med (Lond). 2021 Oct 28;1:43. doi: 10.1038/s43856-021-00043-x. eCollection 2021.

ABSTRACT

BACKGROUND: Artificial intelligence can assist in interpreting chest X-ray radiography (CXR) data, but large datasets require efficient image annotation. The purpose of this study is to extract CXR labels from diagnostic reports based on natural language processing, train convolutional neural networks (CNNs), and evaluate the classification performance of CNN using CXR data from multiple centers.

METHODS: We collected the CXR images and corresponding radiology reports of 74,082 subjects as the training dataset. The linguistic entities and relationships from unstructured radiology reports were extracted by the bidirectional encoder representations from transformers (BERT) model, and a knowledge graph was constructed to represent the association between image labels of abnormal signs and the report text of CXR. Then, a 25-label classification system were built to train and test the CNN models with weakly supervised labeling.

RESULTS: In three external test cohorts of 5,996 symptomatic patients, 2,130 screening examinees, and 1,804 community clinic patients, the mean AUC of identifying 25 abnormal signs by CNN reaches 0.866 ± 0.110, 0.891 ± 0.147, and 0.796 ± 0.157, respectively. In symptomatic patients, CNN shows no significant difference with local radiologists in identifying 21 signs (p > 0.05), but is poorer for 4 signs (p < 0.05). In screening examinees, CNN shows no significant difference for 17 signs (p > 0.05), but is poorer at classifying nodules (p = 0.013). In community clinic patients, CNN shows no significant difference for 12 signs (p > 0.05), but performs better for 6 signs (p < 0.001).

CONCLUSION: We construct and validate an effective CXR interpretation system based on natural language processing.

PMID:35602222 | PMC:PMC9053275 | DOI:10.1038/s43856-021-00043-x

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Antigen and Cell-Based Assays for the Detection of Non-HLA Antibodies

Front Immunol. 2022 May 6;13:864671. doi: 10.3389/fimmu.2022.864671. eCollection 2022.

ABSTRACT

To date, human leukocyte antigens (HLA) have been the major focus in the approach to acute and chronic antibody-mediated rejection (AMBR) in solid-organ transplantation. However, evidence from the clinic and published studies has shown that non-HLA antibodies, particularly anti-endothelial cell antibodies (AECAs), are found either in the context of AMBR or synergistically in the presence of donor-specific anti-HLA antibodies (DSA). Numerous studies have explored the influence of AECAs on clinical outcomes, yet the determination of the exact clinical relevance of non-HLA antibodies in organ transplantation is not fully established. This is due to highly heterogeneous study designs including differences in testing methods and outcome measures. Efforts to develop reliable and sensitive diagnostic non-HLA antibody tests are continuously made. This is essential considering the technical difficulties of non-HLA antibody assays and the large variation in reported incidences of antibodies. In addition, it is important to take donor specificity into account in order to draw clinically relevant conclusions from non-HLA antibody assays. Here, we provide an overview of non-HLA solid-phase and cell-based crossmatch assays for use in solid-organ transplantation that are currently available, either in a research setting or commercially.

PMID:35603145 | PMC:PMC9122123 | DOI:10.3389/fimmu.2022.864671

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Dynamic modulation of neural feedback processing and attention during spatial probabilistic learning

iScience. 2022 Apr 25;25(5):104302. doi: 10.1016/j.isci.2022.104302. eCollection 2022 May 20.

ABSTRACT

Learned stimulus-reward associations can modulate behavior and the underlying neural processing of information. We investigated the cascade of these neurocognitive mechanisms involved in the learning of spatial stimulus-reward associations. Using electroencephalogram recordings while participants performed a probabilistic spatial reward learning task, we observed that the feedback-related negativity component was more negative in response to loss feedback compared to gain feedback but showed no modulation by learning. The late positive component became larger in response to losses as the learning set progressed but smaller in response to gains. In addition, feedback-locked alpha frequency oscillations measured over occipital sites were predictive of N2pc amplitudes-a marker of spatial attention orienting-observed on the next trial. This relationship was found to become stronger with learning set progression. Taken together, we elucidated neurocognitive dynamics underlying feedback processing during spatial reward learning, and the subsequent effects of these learned spatial stimulus-reward associations on spatial attention.

PMID:35602968 | PMC:PMC9118728 | DOI:10.1016/j.isci.2022.104302

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