em Cholesterol Management By www.medicinenet.com Published On :: Wed, 6 Jul 2022 00:00:00 PDT Title: Cholesterol ManagementCategory: Diseases and ConditionsCreated: 12/31/1997 12:00:00 AMLast Editorial Review: 7/6/2022 12:00:00 AM Full Article
em Even Chores, Socializing Might Lower Your Odds for Dementia By www.medicinenet.com Published On :: Fri, 29 Jul 2022 00:00:00 PDT Title: Even Chores, Socializing Might Lower Your Odds for DementiaCategory: Health NewsCreated: 7/28/2022 12:00:00 AMLast Editorial Review: 7/29/2022 12:00:00 AM Full Article
em Lifestyle May Be Key to Helping You Avoid Dementia By www.medicinenet.com Published On :: Fri, 5 Aug 2022 00:00:00 PDT Title: Lifestyle May Be Key to Helping You Avoid DementiaCategory: Health NewsCreated: 8/4/2022 12:00:00 AMLast Editorial Review: 8/5/2022 12:00:00 AM Full Article
em Abnormal Upper Heart Chamber May Boost Dementia Risk By www.medicinenet.com Published On :: Wed, 10 Aug 2022 00:00:00 PDT Title: Abnormal Upper Heart Chamber May Boost Dementia RiskCategory: Health NewsCreated: 8/10/2022 12:00:00 AMLast Editorial Review: 8/10/2022 12:00:00 AM Full Article
em Everyday Activities That Can Cut Your Odds for Dementia By www.medicinenet.com Published On :: Mon, 15 Aug 2022 00:00:00 PDT Title: Everyday Activities That Can Cut Your Odds for DementiaCategory: Health NewsCreated: 8/12/2022 12:00:00 AMLast Editorial Review: 8/15/2022 12:00:00 AM Full Article
em Brain Zaps Give Month-Long Memory Boost By www.medicinenet.com Published On :: Tue, 23 Aug 2022 00:00:00 PDT Title: Brain Zaps Give Month-Long Memory BoostCategory: Health NewsCreated: 8/22/2022 12:00:00 AMLast Editorial Review: 8/23/2022 12:00:00 AM Full Article
em AHA News: People With Dementia May Be Less Likely to Receive an Advanced Treatment For Stroke By www.medicinenet.com Published On :: Wed, 24 Aug 2022 00:00:00 PDT Title: AHA News: People With Dementia May Be Less Likely to Receive an Advanced Treatment For StrokeCategory: Health NewsCreated: 8/24/2022 12:00:00 AMLast Editorial Review: 8/24/2022 12:00:00 AM Full Article
em Magic Mushroom Hallucinogen May Treat Problem Drinking By www.medicinenet.com Published On :: Thu, 25 Aug 2022 00:00:00 PDT Title: Magic Mushroom Hallucinogen May Treat Problem DrinkingCategory: Health NewsCreated: 8/24/2022 12:00:00 AMLast Editorial Review: 8/25/2022 12:00:00 AM Full Article
em Banded Squats: Benefits and 11 Ways to Do Them By www.medicinenet.com Published On :: Mon, 8 Aug 2022 00:00:00 PDT Title: Banded Squats: Benefits and 11 Ways to Do ThemCategory: Health and LivingCreated: 8/8/2022 12:00:00 AMLast Editorial Review: 8/8/2022 12:00:00 AM Full Article
em Dietary Supplements: Are You Throwing Money Away? By www.medicinenet.com Published On :: Tue, 2 Aug 2022 00:00:00 PDT Title: Dietary Supplements: Are You Throwing Money Away?Category: Health NewsCreated: 8/2/2022 12:00:00 AMLast Editorial Review: 8/2/2022 12:00:00 AM Full Article
em FDA Warns Amazon, Other Vendors About Sale of Skin Tag Removal Products By www.medicinenet.com Published On :: Wed, 10 Aug 2022 00:00:00 PDT Title: FDA Warns Amazon, Other Vendors About Sale of Skin Tag Removal ProductsCategory: Health NewsCreated: 8/10/2022 12:00:00 AMLast Editorial Review: 8/10/2022 12:00:00 AM Full Article
em As Pandemic Eases, It's Boom Times for Cosmetic Surgeons By www.medicinenet.com Published On :: Wed, 24 Aug 2022 00:00:00 PDT Title: As Pandemic Eases, It's Boom Times for Cosmetic SurgeonsCategory: Health NewsCreated: 8/24/2022 12:00:00 AMLast Editorial Review: 8/24/2022 12:00:00 AM Full Article
em What Are the Main Parts of the Male Reproductive System? By www.medicinenet.com Published On :: Thu, 7 Jul 2022 00:00:00 PDT Title: What Are the Main Parts of the Male Reproductive System?Category: Diseases and ConditionsCreated: 7/7/2022 12:00:00 AMLast Editorial Review: 7/7/2022 12:00:00 AM Full Article
em Prostate Problems By www.medicinenet.com Published On :: Thu, 21 Jul 2022 00:00:00 PDT Title: Prostate ProblemsCategory: Diseases and ConditionsCreated: 10/16/2002 12:00:00 AMLast Editorial Review: 7/21/2022 12:00:00 AM Full Article
em Blood in Semen By www.medicinenet.com Published On :: Fri, 12 Aug 2022 00:00:00 PDT Title: Blood in SemenCategory: Diseases and ConditionsCreated: 12/31/1997 12:00:00 AMLast Editorial Review: 8/12/2022 12:00:00 AM Full Article
em Pets Have Helped People With HIV Through Two Pandemics By www.medicinenet.com Published On :: Thu, 23 Jun 2022 00:00:00 PDT Title: Pets Have Helped People With HIV Through Two PandemicsCategory: Health NewsCreated: 6/23/2022 12:00:00 AMLast Editorial Review: 6/23/2022 12:00:00 AM Full Article
em HIV Testing Plummeted During Pandemic By www.medicinenet.com Published On :: Mon, 27 Jun 2022 00:00:00 PDT Title: HIV Testing Plummeted During PandemicCategory: Health NewsCreated: 6/27/2022 12:00:00 AMLast Editorial Review: 6/27/2022 12:00:00 AM Full Article
em furosemide By www.medicinenet.com Published On :: Wed, 10 Aug 2022 00:00:00 PDT Title: furosemideCategory: MedicationsCreated: 12/31/1997 12:00:00 AMLast Editorial Review: 8/10/2022 12:00:00 AM Full Article
em Self-Employed Women Are Often Healthier: Study By www.medicinenet.com Published On :: Mon, 8 Aug 2022 00:00:00 PDT Title: Self-Employed Women Are Often Healthier: StudyCategory: Health NewsCreated: 8/8/2022 12:00:00 AMLast Editorial Review: 8/8/2022 12:00:00 AM Full Article
em When Removing a Big Kidney Stone, Get the Little Ones, Too By www.medicinenet.com Published On :: Thu, 11 Aug 2022 00:00:00 PDT Title: When Removing a Big Kidney Stone, Get the Little Ones, TooCategory: Health NewsCreated: 8/11/2022 12:00:00 AMLast Editorial Review: 8/11/2022 12:00:00 AM Full Article
em Pot Users Are Less Prone to Sinus Problems By www.medicinenet.com Published On :: Tue, 2 Aug 2022 00:00:00 PDT Title: Pot Users Are Less Prone to Sinus ProblemsCategory: Health NewsCreated: 8/1/2022 12:00:00 AMLast Editorial Review: 8/2/2022 12:00:00 AM Full Article
em Study Casts Doubt on 'Chemical Imbalance' Theory of Depression By www.medicinenet.com Published On :: Tue, 9 Aug 2022 00:00:00 PDT Title: Study Casts Doubt on 'Chemical Imbalance' Theory of DepressionCategory: Health NewsCreated: 8/9/2022 12:00:00 AMLast Editorial Review: 8/9/2022 12:00:00 AM Full Article
em Evidence-based management of symptoms in serious respiratory illness: what is in our toolbox? By err.ersjournals.com Published On :: 2024-10-30T01:30:15-07:00 Extract Living with a respiratory illness requires patients to manage a wide range of symptoms, many of which will worsen as a disease progresses. Breathlessness is a hallmark feature of respiratory conditions, occurring in almost all individuals with COPD and interstitial lung disease (ILD) [1, 2]. Cough is present in 78% of people with ILD and is frequently distressing, with physical, social and emotional impacts [1, 3]. Full Article
em Impaired lung function and associated risk factors in children born prematurely: a systematic review and meta-analysis By err.ersjournals.com Published On :: 2024-10-09T00:15:15-07:00 Background Immature lung development and respiratory morbidity place preterm-born children at high risk of long-term pulmonary sequelae. This systematic review and meta-analysis aims to quantify lung function in preterm-born children and identify risk factors for a compromised lung function. Methods We searched MEDLINE, Embase, Cochrane Library, Web of Science and Scopus for relevant studies published on preterm cohorts born since 1990. Studies comparing forced expiratory volume in 1 s (FEV1) in preterm-born children aged ≥5 years to term-born controls or normative data were included. Study quality was assessed using the Newcastle–Ottawa Scale for cohort studies. Standardised mean differences in FEV1 and secondary spirometry outcomes per study were pooled using meta-analysis. The impact of different demographic and neonatal variables on studies’ FEV1 effect sizes was investigated by meta-regression analyses. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Results We identified 42 studies with unique cohorts including 4743 preterm children and 9843 controls. Median gestational age in the studies was 28.0 weeks and age at assessment ranged from 6.7 to 16.7 years. Preterm children had lower FEV1 than controls (–0.58 sd, 95% CI –0.69– –0.47 sd, p<0.001) resulting in a relative risk of 2.9 (95% CI 2.4–3.4) for abnormal outcome, with high certainty of evidence. FEV1 was significantly associated with gestational age, birthweight, bronchopulmonary dysplasia and invasive mechanical ventilation in univariate meta-regression analyses (R2=36–96%). Conclusion This systematic review shows robust evidence of impaired lung function in preterm-born children with a high certainty of evidence. Full Article
em Epidemiology of severe asthma in children: a systematic review and meta-analysis By err.ersjournals.com Published On :: 2024-10-09T00:15:15-07:00 Background Severe asthma significantly impacts a minority of children with asthma, leading to frequent symptoms, hospitalisations and potential long-term health consequences. However, accurate global data on severe asthma epidemiology is lacking. This study aims to address this gap, providing data on severe asthma epidemiology, regional differences and associated comorbidities. Methods We conducted a rigorous systematic review and meta-analysis following a registered protocol (PROSPERO CRD42023472845). We searched PubMed, Scopus and Web of Science for cohort or cross-sectional studies published since 2003, evaluating severe asthma incidence and prevalence in children. Study quality and risk of bias were assessed using STROBE guidelines. Results Nine studies investigating European children with asthma (aged 5–18 years) were included in the meta-analysis. No significant publication bias was found. The overall severe asthma prevalence in children with asthma was 3% (95% CI 1–6; I2=99.9%; p<0.001), with no significant difference between males and females. Prevalence estimates varied significantly depending on the diagnostic criteria used (Global Initiative for Asthma: 6%; European Respiratory Society/American Thoracic Society: 1%; other: 3%). Because none of the examined studies were prospectively designed, incidence rates could not be determined. Conclusions This systematic review and meta-analysis provide the first robust assessment of severe asthma prevalence among European children. Our findings underscore the need for comprehensive research to address knowledge gaps in severe asthma, including determining incidence rates, standardising definitions, investigating regional differences and evaluating comorbidities and treatment strategies. Full Article
em Epidemiology of bronchiectasis By err.ersjournals.com Published On :: 2024-10-09T00:15:15-07:00 Bronchiectasis is a chronic respiratory disease characterised by permanent enlargement of the airways associated with cough, sputum production and a history of pulmonary exacerbations. In the past few years, incidence and prevalence of bronchiectasis have increased worldwide, possibly due to advances in imaging techniques and disease awareness, leading to increased socioeconomic burden and healthcare costs. Consistently, a mortality increase in bronchiectasis patient cohorts has been demonstrated in certain areas of the globe, with mortality rates of 16–24.8% over 4–5 years of follow-up. However, heterogeneity in epidemiological data is consistent, as reported prevalence in the general population ranges from 52.3 to more than 1000 per 100 000. Methodological flaws in the designs of available studies are likely to underestimate the proportion of people suffering from this condition worldwide and comparisons between different areas of the globe might be unreliable due to different assessment methods or local implementation of the same method in different contexts. Differences in disease severity associated with diverse geographical distribution of aetiologies, comorbidities and microbiology might explain an additional quota of heterogeneity. Finally, limited access to care in certain geographical areas is associated with both underestimation of the disease and increased severity and mortality. The aim of this review is to provide a snapshot of available real-world epidemiological data describing incidence and prevalence of bronchiectasis in the general population. Furthermore, data on mortality, healthcare burden and high-risk populations are provided. Finally, an analysis of the geographical distribution of determinants contributing to differences in bronchiectasis epidemiology is offered. Full Article
em Multicomponent services for symptoms in serious respiratory illness: a systematic review and meta-analysis By err.ersjournals.com Published On :: 2024-10-30T01:30:15-07:00 Background People living with serious respiratory illness experience a high burden of symptoms. This review aimed to determine whether multicomponent services reduce symptoms in people with serious illness related to respiratory disease. Methods Electronic databases were searched to identify randomised controlled trials (RCTs) evaluating multicomponent services that enrolled patients due to symptoms, rather than underlying disease, and provided at least one nonpharmacological intervention. The primary outcome was chronic breathlessness and secondary outcomes were health-related quality of life (HRQoL), cough, fatigue and adverse events. At least two authors independently screened studies, assessed risk of bias and extracted data. Results Five RCTs, involving 439 patients, were included. In comparison to usual care, multicomponent services improved breathlessness mastery (Chronic Respiratory Questionnaire (CRQ) mastery scale, mean difference (MD) 0.43 points, 95% CI 0.20–0.67, three RCTs, 327 participants) and HRQoL (CRQ total score, MD 0.24 points, 95% CI 0.04–0.40, two RCTs, 237 participants). Fatigue did not improve with multicomponent services and no studies evaluated cough. No serious adverse events were reported. The one study evaluating mortality found increased survival in those accessing a multicomponent service. The certainty of evidence was very low, mainly due to detection and reporting bias. Conclusion Multicomponent services improve breathlessness mastery and HRQoL, with minimal risk. These findings support the use of multicomponent symptom-directed services for people living with serious respiratory illness. Full Article
em The effect of graded exercise therapy on fatigue in people with serious respiratory illness: a systematic review By err.ersjournals.com Published On :: 2024-10-09T00:15:15-07:00 Background In adults with serious respiratory illness, fatigue is prevalent and under-recognised, with few treatment options. The aim of this review was to assess the impact of graded exercise therapy (GET) on fatigue in adults with serious respiratory illness. Methods Electronic databases were searched to identify randomised controlled trials (RCTs) testing GET (involving incremental increases in exercise from an established baseline) in adults with serious respiratory illness. The primary outcome was fatigue and secondary outcomes were health-related quality of life (HRQoL) and adverse events. Two authors independently screened for inclusion, evaluated risk of bias and extracted data. Results 76 RCTs were included with 3309 participants, most with a diagnosis of COPD or asthma. Reductions in fatigue measured by the Chronic Respiratory Disease Questionnaire fatigue domain score were demonstrated following GET consisting of aerobic with/without resistance training (mean difference (MD) 0.53 points, 95% CI 0.41–0.65, 11 RCTs, 624 participants) and GET using resistance training alone (MD 0.58 points, 95% CI 0.21–0.96, two RCTs, 82 participants) compared with usual care. Although the mean effect exceeded the minimal important difference, the lower end of the confidence intervals did not always exceed this threshold so the clinical significance could not be confirmed. GET consistently improved HRQoL in people with a range of chronic respiratory diseases on multiple HRQoL measures. No serious adverse events related to GET were reported. Conclusion GET may improve fatigue alongside consistent improvements in HRQoL in people with serious respiratory illness. These findings support the use of GET in the care of people with serious respiratory illness. Full Article
em Breathing techniques to reduce symptoms in people with serious respiratory illness: a systematic review By err.ersjournals.com Published On :: 2024-10-30T01:30:15-07:00 Background In adults with serious respiratory illness, breathlessness is prevalent and associated with reduced health-related quality of life. The aim of this review was to assess the impact of breathing techniques on breathlessness in adults with serious respiratory illness. Methods Electronic databases were searched to identify randomised controlled trials testing breathing techniques (techniques that aim to alter the respiratory pattern, excluding respiratory muscle training) in people with serious respiratory illness. The primary outcome was breathlessness and secondary outcomes were health-related quality of life and adverse events. Two authors independently screened for inclusion, evaluated risk of bias and extracted data. Results 73 randomised controlled trials were included with 5479 participants, most with COPD or asthma. Breathing exercises (pursed lip and/or diaphragmatic breathing) reduced breathlessness measured by the modified Medical Research Council scale compared to usual care (mean difference (MD) –0.40 points, 95% CI –0.70– –0.11, eight studies, n=323), although the effect did not exceed the minimal important difference. Yoga breathing also improved modified Medical Research Council score compared to usual care (MD –1.05 points, 95% CI –2.45–0.35, three studies, n=175). Breathing techniques consistently improved health-related quality of life in people with COPD and asthma on multiple health-related quality of life measures in comparison to usual care, with effects that generally exceeded the minimal important difference. No adverse events related to breathing techniques were reported. Conclusion Breathing techniques may improve breathlessness, and consistently improve health-related quality of life, in people with serious respiratory illness. These findings support the use of breathing exercises in the care of people with serious respiratory illness. Full Article
em Opioids for the palliation of symptoms in people with serious respiratory illness: a systematic review and meta-analysis By err.ersjournals.com Published On :: 2024-10-09T00:15:15-07:00 Background People living with serious respiratory illness experience a high burden of distressing symptoms. Although opioids are prescribed for symptom management, they generate adverse events, and their benefits are unclear. Methods We examined the efficacy and safety of opioids for symptom management in people with serious respiratory illness. Embase, MEDLINE and the Cochrane Central Register of Controlled Trials were searched up to 11 July 2022. Reports of randomised controlled trials administering opioids to treat symptoms in people with serious respiratory illness were included. Key exclusion criteria included <80% of participants having a nonmalignant lung disease. Data were extracted regarding study characteristics, outcomes of breathlessness, cough, health-related quality of life (HRQoL) and adverse events. Treatment effects were pooled using a generic inverse variance model with random effects. Risk of bias was assessed using the Cochrane Risk of Bias tool version 1. Results Out of 17 included trials, six were laboratory-based exercise trials (n=70), 10 were home studies measuring breathlessness in daily life (n=788) and one (n=18) was conducted in both settings. Overall certainty of evidence was "very low" to "low". Opioids reduced breathlessness intensity during laboratory exercise testing (standardised mean difference (SMD) –0.37, 95% CI –0.67– –0.07), but not breathlessness measured in daily life (SMD –0.10, 95% CI –0.64–0.44). No effects on HRQoL (SMD –0.42, 95% CI –0.98–0.13) or cough (SMD –1.42, 95% CI –3.99–1.16) were detected. In at-home studies, opioids led to increased frequency of nausea/vomiting (OR 3.32, 95% CI 1.70–6.51), constipation (OR 3.08, 95% CI 1.69–5.61) and drowsiness (OR 1.37, 95% CI 1.01–1.86), with serious adverse events including hospitalisation and death identified. Conclusions Opioids improved exertional breathlessness in laboratory exercise studies, but did not improve breathlessness, cough or HRQoL measured in daily life at home. There were significant adverse events, which may outweigh any benefits. Full Article
em Systematic identification of interchromosomal interaction networks supports the existence of specialized RNA factories [METHODS] By genome.cshlp.org Published On :: 2024-10-29T06:46:08-07:00 Most studies of genome organization have focused on intrachromosomal (cis) contacts because they harbor key features such as DNA loops and topologically associating domains. Interchromosomal (trans) contacts have received much less attention, and tools for interrogating potential biologically relevant trans structures are lacking. Here, we develop a computational framework that uses Hi-C data to identify sets of loci that jointly interact in trans. This method, trans-C, initiates probabilistic random walks with restarts from a set of seed loci to traverse an input Hi-C contact network, thereby identifying sets of trans-contacting loci. We validate trans-C in three increasingly complex models of established trans contacts: the Plasmodium falciparum var genes, the mouse olfactory receptor "Greek islands," and the human RBM20 cardiac splicing factory. We then apply trans-C to systematically test the hypothesis that genes coregulated by the same trans-acting element (i.e., a transcription or splicing factor) colocalize in three dimensions to form "RNA factories" that maximize the efficiency and accuracy of RNA biogenesis. We find that many loci with multiple binding sites of the same DNA-binding proteins interact with one another in trans, especially those bound by factors with intrinsically disordered domains. Similarly, clustered binding of a subset of RNA-binding proteins correlates with trans interaction of the encoding loci. We observe that these trans-interacting loci are close to nuclear speckles. These findings support the existence of trans-interacting chromatin domains (TIDs) driven by RNA biogenesis. Trans-C provides an efficient computational framework for studying these and other types of trans interactions, empowering studies of a poorly understood aspect of genome architecture. Full Article
em Complete genomes of Asgard archaea reveal diverse integrated and mobile genetic elements [RESEARCH] By genome.cshlp.org Published On :: 2024-10-29T06:46:08-07:00 Asgard archaea are of great interest as the progenitors of Eukaryotes, but little is known about the mobile genetic elements (MGEs) that may shape their ongoing evolution. Here, we describe MGEs that replicate in Atabeyarchaeia, a wetland Asgard archaea lineage represented by two complete genomes. We used soil depth–resolved population metagenomic data sets to track 18 MGEs for which genome structures were defined and precise chromosome integration sites could be identified for confident host linkage. Additionally, we identified a complete 20.67 kbp circular plasmid and two family-level groups of viruses linked to Atabeyarchaeia, via CRISPR spacer targeting. Closely related 40 kbp viruses possess a hypervariable genomic region encoding combinations of specific genes for small cysteine-rich proteins structurally similar to restriction-homing endonucleases. One 10.9 kbp integrative conjugative element (ICE) integrates genomically into the Atabeyarchaeum deiterrae-1 chromosome and has a 2.5 kbp circularizable element integrated within it. The 10.9 kbp ICE encodes an expressed Type IIG restriction-modification system with a sequence specificity matching an active methylation motif identified by Pacific Biosciences (PacBio) high-accuracy long-read (HiFi) metagenomic sequencing. Restriction-modification of Atabeyarchaeia differs from that of another coexisting Asgard archaea, Freyarchaeia, which has few identified MGEs but possesses diverse defense mechanisms, including DISARM and Hachiman, not found in Atabeyarchaeia. Overall, defense systems and methylation mechanisms of Asgard archaea likely modulate their interactions with MGEs, and integration/excision and copy number variation of MGEs in turn enable host genetic versatility. Full Article
em De novo genome assemblies of two cryptodiran turtles with ZZ/ZW and XX/XY sex chromosomes provide insights into patterns of genome reshuffling and uncover novel 3D genome folding in amniotes [RESEARCH] By genome.cshlp.org Published On :: 2024-10-29T06:46:07-07:00 Understanding the evolution of chromatin conformation among species is fundamental to elucidate the architecture and plasticity of genomes. Nonrandom interactions of linearly distant loci regulate gene function in species-specific patterns, affecting genome function, evolution, and, ultimately, speciation. Yet, data from nonmodel organisms are scarce. To capture the macroevolutionary diversity of vertebrate chromatin conformation, here we generate de novo genome assemblies for two cryptodiran (hidden-neck) turtles via Illumina sequencing, chromosome conformation capture, and RNA-seq: Apalone spinifera (ZZ/ZW, 2n = 66) and Staurotypus triporcatus (XX/XY, 2n = 54). We detected differences in the three-dimensional (3D) chromatin structure in turtles compared to other amniotes beyond the fusion/fission events detected in the linear genomes. Namely, whole-genome comparisons revealed distinct trends of chromosome rearrangements in turtles: (1) a low rate of genome reshuffling in Apalone (Trionychidae) whose karyotype is highly conserved when compared to chicken (likely ancestral for turtles), and (2) a moderate rate of fusions/fissions in Staurotypus (Kinosternidae) and Trachemys scripta (Emydidae). Furthermore, we identified a chromosome folding pattern that enables "centromere–telomere interactions" previously undetected in turtles. The combined turtle pattern of "centromere–telomere interactions" (discovered here) plus "centromere clustering" (previously reported in sauropsids) is novel for amniotes and it counters previous hypotheses about amniote 3D chromatin structure. We hypothesize that the divergent pattern found in turtles originated from an amniote ancestral state defined by a nuclear configuration with extensive associations among microchromosomes that were preserved upon the reshuffling of the linear genome. Full Article
em Mutational scanning of CRX classifies clinical variants and reveals biochemical properties of the transcriptional effector domain [RESEARCH] By genome.cshlp.org Published On :: 2024-10-29T06:46:07-07:00 The transcription factor (TF) cone-rod homeobox (CRX) is essential for the differentiation and maintenance of photoreceptor cell identity. Several human CRX variants cause degenerative retinopathies, but most are variants of uncertain significance. We performed a deep mutational scan (DMS) of nearly all possible single amino acid substitutions in CRX using a cell-based transcriptional reporter assay, curating a high-confidence list of nearly 2000 variants with altered transcriptional activity. In the structured homeodomain, activity scores closely aligned to a predicted structure and demonstrated position-specific constraints on amino acid substitution. In contrast, the intrinsically disordered transcriptional effector domain displayed a qualitatively different pattern of substitution effects, following compositional constraints without specific residue position requirements in the peptide chain. These compositional constraints were consistent with the acidic exposure model of transcriptional activation. We evaluated the performance of the DMS assay as a clinical variant classification tool using gold-standard classified human variants from ClinVar, identifying pathogenic variants with high specificity and moderate sensitivity. That this performance could be achieved using a synthetic reporter assay in a foreign cell type, even for a highly cell type-specific TF like CRX, suggests that this approach shows promise for DMS of other TFs that function in cell types that are not easily accessible. Together, the results of the CRX DMS identify molecular features of the CRX effector domain and demonstrate utility for integration into the clinical variant classification pipeline. Full Article
em Evidence for compensatory evolution within pleiotropic regulatory elements [RESEARCH] By genome.cshlp.org Published On :: 2024-10-29T06:46:07-07:00 Pleiotropy, measured as expression breadth across tissues, is one of the best predictors for protein sequence and expression conservation. In this study, we investigated its effect on the evolution of cis-regulatory elements (CREs). To this end, we carefully reanalyzed the Epigenomics Roadmap data for nine fetal tissues, assigning a measure of pleiotropic degree to nearly half a million CREs. To assess the functional conservation of CREs, we generated ATAC-seq and RNA-seq data from humans and macaques. We found that more pleiotropic CREs exhibit greater conservation in accessibility, and the mRNA expression levels of the associated genes are more conserved. This trend of higher conservation for higher degrees of pleiotropy persists when analyzing the transcription factor binding repertoire. In contrast, simple DNA sequence conservation of orthologous sites between species tends to be even lower for pleiotropic CREs than for species-specific CREs. Combining various lines of evidence, we propose that the lack of sequence conservation in functionally conserved pleiotropic CREs is owing to within-element compensatory evolution. In summary, our findings suggest that pleiotropy is also a good predictor for the functional conservation of CREs, even though this is not reflected in the sequence conservation of pleiotropic CREs. Full Article
em Impact of COVID-19 on Chronic Ambulatory-Care-Sensitive Condition Emergency Department Use Among Older Adults By www.jabfm.org Published On :: 2024-10-25T09:26:14-07:00 Background: The COVID-19 pandemic social distancing requirements encouraged patients to avoid public spaces including in-office health care visits. Ambulatory-care-sensitive conditions (ACSCs) represent conditions that can be managed with quality primary care and when access is limited, these conditions can lead to avoidable emergency department (ED) visits. Methods: Using national data on ED visits from 2019 to 2021 in the National Hospital Ambulatory Care Survey, we examined the impact of COVID-19 pandemic on ACSC ED visits among older adults (aged ≥65). Results: The proportion of ED visits among older adults that were for ACSCs increased between 2019 (17.4%) and 2021 (18.5%). The trend in both rural (26.4%–28.6%) and urban areas (15.4%–16.8%) shows a significant jump from 2019 to 2021 (P < .001). Conclusions: This rise in ACSC ED use is consistent with a delay in normal primary care during the pandemic. Full Article
em Impact of Point of Care Hemoglobin A1c Testing on Time to Therapeutic Intervention By www.jabfm.org Published On :: 2024-10-25T09:26:14-07:00 Without compromising accuracy, point of care testing (POCT) provides immediate results at the time of in person patient consultation. The purpose of this study was to evaluate time until therapeutic intervention with POCT HbA1c versus venipuncture, where venipuncture was considered standard of care. The primary outcome was time (hours) to implementation of a therapeutic intervention based on POCT HbA1c result, as compared with most recent venipuncture HbA1c before the study and its associated therapeutic intervention. A total of 94 POCT HbA1c tests were included in the primary analysis. For the POCT HbA1c, the mean time to therapeutic intervention was 1.6 ± 3.14 hours. For the previous venipuncture HbA1c, the mean time to therapeutic intervention was 1376.66 ± 3356.6 hours (P < .001). Overall, this trial showed that POCT HbA1c results in a significantly faster time to therapeutic intervention than venipuncture in a primary care clinic that serves a rural population. Full Article
em Cannabis and Pain Management By www.jabfm.org Published On :: 2024-10-25T09:26:14-07:00 Family physicians are fielding questions about cannabis --particularly for the use of cannabis for treatment of pain. Like about every substance ingested to treat medical conditions, cannabis has risks and benefits. But regarding evidence-based practice and practice-based recommendations for patients about cannabis use, the cart is in front of the horse. Cannabis use is still illegal at a federal level and a Schedule 1 drug, but most states have challenged federal law by decriminalizing or legalizing cannabis for a variety of uses. Research is difficult due to this federal status as a Schedule 1 drug since federal funding is not readily available to support research. As a result, physicians have little to no guidance about the clinical usefulness of the product. This article explores what we know and what we are learning about cannabis, and the authors provide clinical guidance for patient care based on this evidence. Full Article
em Be SMART About Asthma Management: Single Maintenance and Reliever Therapy By www.jabfm.org Published On :: 2024-10-25T09:26:14-07:00 Single maintenance and reliever therapy (SMART) is an asthma treatment approach that utilizes combined inhaled corticosteroids and long-acting β-agonists for maintenance and quick relief therapy. Despite the evidence for its benefits in asthma treatment and its adoption into American and international asthma guidelines and recommendations, SMART remains a practice of some debate. This article reviews the available evidence for SMART and offers guidance for its integration into comprehensive asthma management. Overall, short-acting β-agonist-only asthma therapy regimens should be avoided, regardless of condition severity (SOR A Recommendation). Family medicine clinicians should start SMART for patients requiring either GINA Step 3 or 4 therapy, especially if they have signs of poor adherence (SOR B Recommendation). Finally, use budesonide-formoterol over other inhaled corticosteroid/long-acting β-agonist combinations when implementing SMART (SOR B Recommendation). Full Article
em Assessing Patient Readiness for Hospital Discharge, Discharge Communication, and Transitional Care Management By www.jabfm.org Published On :: 2024-10-25T09:26:14-07:00 Background: Discharge communication between hospitalists and primary care clinicians is essential to improve care coordination, minimize adverse events, and decrease unplanned health services use. Health-related social needs are key drivers of health, and hospitalists and primary care clinicians value communicating social needs at discharge. Objective: To 1) characterize the current state of discharge communications between an academic medical center hospital and primary care clinicians at associated clinics; 2) seek feedback about the potential usefulness of discharge readiness information to primary care clinicians. Design: Exploratory, convergent mixed methods. Participants: Primary care clinicians from Family Medicine and General Internal Medicine of an academic medical center in the US Intermountain West. Approach: Literature-informed REDCap survey. Semistructured interview guide developed with key informants, grounded in current literature. Survey data were descriptively summarized; interview data were deductively and inductively coded, organized by topics. Results: Two key topics emerged: 1) discharge communication, with interrelated topics of transitional care management and follow-up appointment challenges, and recommendations for improving discharge communication; and 2) usefulness of the discharge readiness information, included interrelated topics related to lack of shared understanding about roles and responsibilities across settings and ethical concerns related to identifying problems that may not have solutions. Conclusions: While reiterating perennial discharge communication and transitional care management challenges, this study reveals new evidence about how these issues are interrelated with assessing and responding to patients’ lack of readiness for discharge and unmet social needs during care transitions. Primary care clinicians had mixed views on the usefulness of discharge readiness information. We offer recommendations for improving discharge communication and transitional care management (TCM) processes, which may be applicable in other care settings. Full Article
em Clinician-Reported Barriers and Needs for Implementation of Continuous Glucose Monitoring By www.jabfm.org Published On :: 2024-10-25T09:26:14-07:00 Background: Continuous glucose monitoring (CGM) for patients with type 1 and type 2 diabetes is associated with improved clinical, behavioral, and psychosocial patient health outcomes and is part of the American Diabetes Association’s Standards of Medical Care. CGM prescription often takes place in endocrinology practices, yet 50% of adults with type 1 diabetes and 90% of all people with type 2 diabetes receive their diabetes care in primary care settings. This study examined primary care clinicians’ perceptions of barriers and resources needed to support CGM use in primary care. Methods: This qualitative study used semistructured interviews with primary care clinicians to understand barriers to CGM and resources needed to prescribe. Participants were recruited through practice-based research networks. Rapid qualitative analysis was used to summarize themes from interview findings. Results: We conducted interviews with 55 primary care clinicians across 21 states. Participants described CGM benefits for patients with varying levels of diabetes self-management and engagement. Major barriers to prescribing included lack of insurance coverage for CGM costs to patients, and time constraints. Participants identified resources needed to foster CGM prescribing, for example, clinician education, support staff, and EHR compatibility. Conclusion: Primary care clinicians face several challenges to prescribing CGM, but they are interested in learning more to help them offer it to their patients. This study reinforces the ongoing need for improved clinician education on CGM technology and continued expansion of insurance coverage for people with both type 1 and type 2 diabetes. Full Article
em Implementation of an Opt-Out Outpatient HIV Screening Program By www.jabfm.org Published On :: 2024-10-25T09:26:14-07:00 Background: Screening rates for Human Immunodeficiency Virus (HIV) remain low despite guidelines by both the CDC and USPSTF recommending that all adolescents and adults be screened at least once. The aim of this quality improvement study was to increase HIV screening among eligible patients. Methods: This quality improvement study assessed the impact of interventions to increase HIV screening in an outpatient population at a large urban safety-net hospital. Outcomes were compared from the preintervention (December 2020 to November 2021) to postintervention years (December 2021 to November 2022). Stepwise electronic alerts to prompt HIV screening paired with provider financial incentives were implemented. The proportion of eligible individuals screened for HIV were compared after intervention implementation. Results: Average monthly HIV screening increased from 506 ± 97 to 2484 ± 663 between the pre- and postintervention periods, correlating to a 5.1-fold increase in screening (7.8% to 39.8%, P < .01). Increases were seen across all ages, and those aged 55 to 64 and 65+ had the highest relative increase in screening at 7.5 and 9.3-fold, respectively (P < .01). Screening rates increased for Hispanics (7.9% preintervention vs 43.6% postintervention, P < .01). In the pre- and postintervention periods, 41 patients with new HIV diagnoses were identified (13 preintervention and 28 postintervention) and 85.4% were linked to care within 30 days. Conclusions: Stepwise interventions targeted at primary care clinicians are an effective way to increase HIV screening rates, particularly in older demographics. Earlier HIV diagnosis coupled with linkage to care is an important strategy in ending the HIV epidemic. Full Article
em Using Primary Health Care Electronic Medical Records to Predict Hospitalizations, Emergency Department Visits, and Mortality: A Systematic Review By www.jabfm.org Published On :: 2024-10-25T09:26:14-07:00 Introduction: High-quality primary care can reduce avoidable emergency department visits and emergency hospitalizations. The availability of electronic medical record (EMR) data and capacities for data storage and processing have created opportunities for predictive analytics. This systematic review examines studies which predict emergency department visits, hospitalizations, and mortality using EMR data from primary care. Methods: Six databases (Ovid MEDLINE, PubMed, Embase, EBM Reviews (Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, Health Technology Assessment, NHS Economic Evaluation Database), Scopus, CINAHL) were searched to identify primary peer-reviewed studies in English from inception to February 5, 2020. The search was initially conducted on January 18, 2019, and updated on February 5, 2020. Results: A total of 9456 citations were double-reviewed, and 31 studies met the inclusion criteria. The predictive ability measured by C-statistics (ROC) of the best performing models from each study ranged from 0.57 to 0.95. Less than half of the included studies used artificial intelligence methods and only 7 (23%) were externally validated. Age, medical diagnoses, sex, medication use, and prior health service use were the most common predictor variables. Few studies discussed or examined the clinical utility of models. Conclusions: This review helps address critical gaps in the literature regarding the potential of primary care EMR data. Despite further work required to address bias and improve the quality and reporting of prediction models, the use of primary care EMR data for predictive analytics holds promise. Full Article
em The Challenge of Implementing Race-Neutral PFT Reference Equations By rc.rcjournal.com Published On :: 2024-10-25T05:44:13-07:00 Full Article
em Effect of Fasting Prior to Extubation on Prevalence of Empty Stomach in Enterally Fed and Mechanically Ventilated Patients By rc.rcjournal.com Published On :: 2024-10-25T05:44:12-07:00 BACKGROUND:Practice on fasting prior to extubation in critically ill patients is variable. Efficacy of fasting in reducing gastric volume has not been well established. The primary objective of this study was to assess the effect of 4 h of fasting on prevalence of empty stomach using gastric ultrasonography in critically ill subjects who are fasted for extubation. The secondary objectives were to evaluate the change in gastric volumes during 4 h of fasting and to determine factors associated with empty stomach after fasting.METHODS:This was a single-center, prospective, observational study on adult ICU subjects who were enterally fed for at least 6 h continuously and mechanically ventilated. Gastric ultrasound was performed immediately prior to commencement of fasting, after 4 h of fasting, and after nasogastric (NG) aspiration after 4 h of fasting. An empty stomach was defined as a gastric volume ≤ 1.5 mL/kg.RESULTS:Forty subjects were recruited, and 38 (95%) had images suitable for analysis. The prevalence of empty stomach increased after 4 h of fasting (25 [65.8%] vs 31 [81.6%], P = .041) and after 4 h of fasting with NG aspiration (25 [65.8%] vs 34 [89.5%], P = .008). There was a significant difference in median (interquartile range) gastric volume per body weight between before fasting and 4 h after fasting (1.0 [0.5–1.8] mL/kg vs 0.4 [0.2–1.0] mL/kg, P < .001). No patient factors were associated with higher prevalence of empty stomach after 4 h of fasting.CONCLUSIONS:Most mechanically ventilated subjects had empty stomachs prior to fasting for extubation. Fasting for 4 h further increased the prevalence of empty stomach at extubation to > 80%. Full Article
em The Impact of Increased PEEP on Hemodynamics, Respiratory Mechanics, and Oxygenation in Pediatric ARDS By rc.rcjournal.com Published On :: 2024-10-25T05:44:12-07:00 BACKGROUND:PEEP is a cornerstone treatment for children with pediatric ARDS. Unfortunately, its titration is often performed solely by evaluating oxygen saturation, which can lead to inadequate PEEP level settings and consequent adverse effects. This study aimed to assess the impact of increasing PEEP on hemodynamics, respiratory system mechanics, and oxygenation in children with ARDS.METHODS:Children receiving mechanical ventilation and on pressure-controlled volume-guaranteed mode were prospectively assessed for inclusion. PEEP was sequentially changed to 5, 12, 10, 8 cm H2O, and again to 5 cm H2O. After 10 min at each PEEP level, hemodynamic, ventilatory, and oxygenation variables were collected.RESULTS:A total of 31 subjects were included, with median age and weight of 6 months and 6.3 kg, respectively. The main reasons for pediatric ICU admission were respiratory failure caused by acute viral bronchiolitis (45%) and community-acquired pneumonia (32%). Most subjects had mild or moderate ARDS (45% and 42%, respectively), with a median (interquartile range) oxygenation index of 8.4 (5.8–12.7). Oxygen saturation improved significantly when PEEP was increased. However, although no significant changes in blood pressure were observed, the median cardiac index at PEEP of 12 cm H2O was significantly lower than that observed at any other PEEP level (P = .001). Fourteen participants (45%) experienced a reduction in cardiac index of > 10% when PEEP was increased to 12 cm H2O. Also, the estimated oxygen delivery was significantly lower, at 12 cm H2O PEEP. Finally, respiratory system compliance significantly reduced when PEEP was increased. At a PEEP of 12 cm H2O, static compliance had a median reduction of 25% in relation to the initial assessment (PEEP of 5 cm H2O).CONCLUSIONS:Although it may improve arterial oxygen saturation, inappropriately high PEEP levels may reduce cardiac output, oxygen delivery, and respiratory system compliance in pediatric subjects with ARDS with low potential for lung recruitability. Full Article
em Invasive Mechanical Ventilation and Risk of Hospital-Acquired Venous Thromboembolism By rc.rcjournal.com Published On :: 2024-10-25T05:44:12-07:00 BACKGROUND:This study sought to estimate the overall cumulative incidence and odds of Hospital-acquired venous thromboembolism (VTE) among critically ill children with and without exposure to invasive ventilation. In doing so, we also aimed to describe the temporal relationship between invasive ventilation and hospital-acquired VTE development.METHODS:We performed a retrospective cohort study using Virtual Pediatric Systems (VPS) data from 142 North American pediatric ICUs among children < 18 y of age from January 1, 2016–December 31, 2022. After exclusion criteria were applied, cohorts were identified by presence of invasive ventilation exposure. The primary outcome was cumulative incidence of hospital-acquired VTE, defined as limb/neck deep venous thrombosis or pulmonary embolism. Multivariate logistic regression was used to determine whether invasive ventilation was an independent risk factor for hospital-acquired VTE development.RESULTS:Of 691,118 children studied, 86,922 (12.4%) underwent invasive ventilation. The cumulative incidence of hospital-acquired VTE for those who received invasive ventilation was 1.9% and 0.12% for those who did not (P < .001). The median time to hospital-acquired VTE after endotracheal intubation was 6 (interquartile range 3–14) d. In multivariate models, invasive ventilation exposure and duration were each independently associated with development of hospital-acquired VTE (adjusted odds ratio 1.64 [95% CI 1.42–1.86], P < .001; and adjusted odds ratio 1.03 [95% CI 1.02–1.03], P < .001, respectively).CONCLUSIONS:In this multi-center retrospective review from the VPS registry, invasive ventilation exposure and duration were independent risk factors for hospital-acquired VTE among critically ill children. Children undergoing invasive ventilation represent an important target population for risk-stratified thromboprophylaxis trials. Full Article
em Rehabilitation Is Associated With Improvements in Post-COVID-19 Sequelae By rc.rcjournal.com Published On :: 2024-10-25T05:44:12-07:00 BACKGROUND:Post–COVID-19 syndrome has affected millions of people, with rehabilitation being at the center of non-pharmacologic care. However, numerous published studies show conflicting results due to, among other factors, considerable variation in subject characteristics. Currently, the effects of age, sex, time of implementation, and prior disease severity on the outcomes of a supervised rehabilitation program after COVID-19 remain unknown.METHODS:This was a non-randomized case-control study. Subjects with post–COVID-19 sequelae were enrolled. Among study participants, those who could attend an 8-week, supervised rehabilitation program composed the intervention group, whereas those who couldn’t the control group. Measurements were collected at baseline and 8 weeks thereafter.RESULTS:Study groups (N = 119) had similar baseline measurements. Participation in rehabilitation (n = 47) was associated with clinically important improvements in the 6-min walk test (6MWT) distance, adjusted (for potential confounders) odds ratio (AOR) 4.56 (95% CI 1.95–10.66); 1-min sit-to-stand test, AOR 4.64 (1.88-11.48); Short Physical Performance Battery, AOR 7.93 (2.82–22.26); health-related quality of life (HRQOL) 5-level EuroQol-5D (Visual Analog Scale), AOR 3.12 (1.37–7.08); Montreal Cognitive Assessment, AOR 6.25 (2.16–18.04); International Physical Activity Questionnaire, AOR 3.63 (1.53–8.59); Fatigue Severity Scale, AOR 4.07 (1.51–10.98); Chalder Fatigue Scale (bimodal score), AOR 3.33 (1.45–7.67); Modified Medical Research Council dyspnea scale (mMRC), AOR 4.43 (1.83–10.74); Post–COVID-19 Functional Scale (PCFS), AOR 3.46 (1.51–7.95); and COPD Assessment Test, AOR 7.40 (2.92–18.75). Time from disease onset was marginally associated only with 6MWT distance, AOR 0.99 (0.99–1.00). Prior hospitalization was associated with clinically important improvements in the mMRC dyspnea scale, AOR 3.50 (1.06–11.51); and PCFS, AOR 3.42 (1.16–10.06). Age, sex, and ICU admission were not associated with the results of any of the aforementioned tests/grading scales.CONCLUSIONS:In this non-randomized, case-control study, post–COVID-19 rehabilitation was associated with improvements in physical function, activity, HRQOL, respiratory symptoms, fatigue, and cognitive impairment. These associations were observed independently of timing of rehabilitation, age, sex, prior hospitalization, and ICU admission. Full Article
em A Review of Artificial Intelligence and Machine Learning in Product Life Cycle Management By journal.pda.org Published On :: 2024-10-22T08:20:35-07:00 The pursuit of harnessing data for knowledge creation has been an enduring quest, with the advent of machine learning (ML) and artificial intelligence (AI) marking significant milestones in this journey. ML, a subset of AI, emerged as the practice of employing mathematical models to enable computers to learn and improve autonomously based on their experiences. In the pharmaceutical and biopharmaceutical sectors, a significant portion of manufacturing data remains untapped or insufficient for practical use. Recognizing the potential advantages of leveraging the available data for process design and optimization, manufacturers face the daunting challenge of data utilization. Diverse proprietary data formats and parallel data generation systems compound the complexity. The transition to Pharma 4.0 necessitates a paradigm shift in data capture, storage, and accessibility for manufacturing and process operations. This paper highlights the pivotal role of AI in converting process data into actionable knowledge to support critical functions throughout the whole product life cycle. Furthermore, it underscores the importance of maintaining compliance with data integrity guidelines, as mandated by regulatory bodies globally. Embracing AI-driven transformations is a crucial step toward shaping the future of the pharmaceutical industry, ensuring its competitiveness and resilience in an evolving landscape. Full Article
em Comparison of Binary Alcohol/Water Solvent Systems to Blood for Extractions of Blood-Contacting Medical Devices By journal.pda.org Published On :: 2024-10-22T08:20:35-07:00 The analysis of extractables and leachables and subsequent risk assessment is an important aspect of the determination of biocompatibility for many medical devices. Leachable chemicals have the potential to pose a toxicological risk to patients, and therefore it is required that they be adequately characterized and assessed for potential safety concerns. One important consideration in the assessment of leachables is the choice of a suitable simulating solvent intended to replicate the use condition for the device and its biological environment. This aspect of study design is especially difficult for blood-contacting medical devices due to the complexity of simulating the biological matrix. This publication reports a comparison of the extracting power of different binary solvent mixtures and saline in comparison with whole blood for a bloodline tubing set connected to a hemodialyzer. Ten different known extractables, spanning a range of physicochemical properties and molecular weights, were quantified. The results indicated that for low-molecular-weight analytes, a suitable exaggeration for whole blood can be obtained using a low-concentration ethanol/water mixture (20%), and in general, extracted quantity increases with the concentration of alcohol cosolvent. For polyvinylpyrrolidone, the opposite trend was observed, as solubility of the polymer was found to decrease with increasing alcohol concentration, resulting in lower extracted quantities at high alcohol concentrations. Analysis of ethanol/water concentrations in the extract solutions post extraction indicated no change in solvent composition. Full Article