Purpose
Many centers perform day‐case cardiac rhythm management (CRM) device implantation. However, there is a paucity of prospective data concerning this approach. We performed a prospective ...single‐center study of day‐case device implantation, including data on patient satisfaction.
Methods
All patients scheduled for a new elective device were considered for a day‐case procedure. Exclusion criteria were living alone or without a suitable carer, advancing age/frailty, a metallic valve, and persistent complete heart block. Following discharge, patients were reviewed in device clinic at 6 weeks with an anonymized questionnaire.
Results
During the study period (May 2014–August 2016), 797 new CRM devices were implanted. Of these, 232 were elective and included in the analysis; 101 were planned to be day‐case and 131 scheduled for overnight stay. Of the 101 day‐case patients, 52 had a pacemaker, 28 an implantable cardioverter defibrillator (ICD), 16 a cardiac resynchronization therapy pacemaker/defibrillator, and five a subcutaneous‐ICD. Complications were similar in the day‐case (n = 12, 12%) and overnight stay (n = 15, 11%) groups (P = 0.92). In the day‐case group, 93 (92%) patients went home the same day. An estimated 111 overnight bed days were saved, translating to a cost saving of £61,912 (euro 70,767, $79,211).
Note that 99% (n = 100) of patients returned the questionnaire. Patient satisfaction was universally high. The majority (n = 98, 98%) felt ready to go home on discharge; only a minority (n = 5, 5%) would have preferred an overnight stay.
Conclusions
A significant proportion of elective new CRM device implants can be performed as day‐case procedures. With appropriate selection patient acceptability of same‐day discharge is high.
Increasing numbers of genes are being implicated in Mendelian disorders and incorporated into clinical test panels. However, lack of evidence supporting the gene-disease relationship can hinder ...interpretation. We explored the utility of testing 51 additional genes for hypertrophic cardiomyopathy (HCM), one of the most commonly tested Mendelian disorders.
Using genome sequencing data from 240 sarcomere gene negative HCM cases and 6229 controls, we undertook case-control and individual variant analyses to assess 51 genes that have been proposed for HCM testing.
We found no evidence to suggest that rare variants in these genes are prevalent causes of HCM. One variant, in a single case, was categorized as likely to be pathogenic. Over 99% of variants were classified as a variant of uncertain significance (VUS) and 54% of cases had one or more VUS.
For almost all genes, the gene-disease relationship could not be validated and lack of evidence precluded variant interpretation. Thus, the incremental diagnostic yield of extending testing was negligible, and would, we propose, be outweighed by problems that arise with a high rate of uninterpretable findings. These findings highlight the need for rigorous, evidence-based selection of genes for clinical test panels.
•Hypothermic preconditioning induced tolerance to hypoxic depolarization and swelling.•Exogenous erythropoietin (EPO) mitigated hypoxic depolarization and swelling.•EPO receptor in bath blocked ...tolerance to hypoxic depolarization and swelling.
We suggested previously that hippocampal slices were protected from hypoxic depolarization and swelling by preincubating them at room temperature (Kreisman et al., 2000). We postulated that hypothermic preconditioning induced tolerance in our slices, which protected against hypoxic depolarization and swelling. Control hippocampal slices were incubated at 34–35 °C for two hours and the response to 10 min of severe hypoxia was compared to slices which were preconditioned for two hours at room temperature (22–23 °C) prior to warming to 34–35 °C. Recordings of the extracellular DC potential provided an index of tissue depolarization and changes in tissue light transmittance provided an index of swelling. Hypothermic preconditioning significantly reduced hypoxia-induced swelling, particularly in CA3 and the dentate inner blade. Since erythropoietin (EPO) had been shown to mediate hypoxic preconditioning, we tested whether EPO also mediated hypothermic preconditioning in our slices. Recombinant rat EPO (1–10 micromolar) mitigated hypoxia-induced swelling and depolarization in dentate inner blade of unconditioned slices in a dose-dependent manner. We also blocked the protective effects of hypothermic preconditioning on hypoxic depolarization and swelling in the inner blade of the dentate gyrus by administering soluble EPO receptor in the bath and treating slices with wortmannin to block phosphorylation of PI3 kinase, a critical step in the activation of the downstream neuroprotectant, Akt. These results suggest that EPO mediates tolerance to hypoxic depolarization and swelling induced by hypothermic preconditioning. They also emphasize that various preincubation protocols used in experiments with hippocampal slices may differentially affect basal electrophysiological and metabolic properties of those slices.
Beginning at the Beginning Campbell, Carolyn; Baikie, Gail
Critical social work,
05/2019, Letnik:
13, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Recognizing the complexities of critical social work the authors use a metaphor of a traffic circle to survey the fundamental values, assumptions, theories, concepts, principles, and practices of ...critical social work. They then consider the relationship among ‘mainstream’, critical, and other marginalized social work perspectives. A subsequent exploration of the challenges and possibilities of critical practice is followed by a reflection on the processes of teaching and learning critical social work. The article does not presume a level of pre-existing social work knowledge or experience on the part of the reader and is therefore accessible and useful for scholars, teachers, students, and practitioners who are new to critical social work.
KEYWORDS: Critical social work; social work education; practice fundamentals
Copy-number changes in 16p11.2 contribute significantly to neuropsychiatric traits. Besides the 600 kb BP4-BP5 CNV found in 0.5%–1% of individuals with autism spectrum disorders and schizophrenia and ...whose rearrangement causes reciprocal defects in head size and body weight, a second distal 220 kb BP2-BP3 CNV is likewise a potent driver of neuropsychiatric, anatomical, and metabolic pathologies. These two CNVs are engaged in complex reciprocal chromatin looping, intimating a functional relationship between genes in these regions that might be relevant to pathomechanism. We assessed the drivers of the distal 16p11.2 duplication by overexpressing each of the nine encompassed genes in zebrafish. Only overexpression of LAT induced a reduction of brain proliferating cells and concomitant microcephaly. Consistently, suppression of the zebrafish ortholog induced an increase of proliferation and macrocephaly. These phenotypes were not unique to zebrafish; Lat knockout mice show brain volumetric changes. Consistent with the hypothesis that LAT dosage is relevant to the CNV pathology, we observed similar effects upon overexpression of CD247 and ZAP70, encoding members of the LAT signalosome. We also evaluated whether LAT was interacting with KCTD13, MVP, and MAPK3, major driver and modifiers of the proximal 16p11.2 600 kb BP4-BP5 syndromes, respectively. Co-injected embryos exhibited an increased microcephaly, suggesting the presence of genetic interaction. Correspondingly, carriers of 1.7 Mb BP1-BP5 rearrangements that encompass both the BP2-BP3 and BP4-BP5 loci showed more severe phenotypes. Taken together, our results suggest that LAT, besides its well-recognized function in T cell development, is a major contributor of the 16p11.2 220 kb BP2-BP3 CNV-associated neurodevelopmental phenotypes.
Background
Noninvasive ventilation (NIV) is the first-line treatment of adult patients with exacerbations of cystic fibrosis (CF). High-flow nasal oxygen therapy (HFNT) might benefit patients with ...hypoxemia and can reduce physiological dead space. We hypothesized that HFNT and NIV would similarly reduce work of breathing and improving breathing pattern in CF patients. Our objective was to compare the effects of HFNT versus NIV in terms of work of breathing, assessed noninvasively by the thickening fraction of the diaphragm (TFdi, measured with ultrasound), breathing pattern, transcutaneous CO
2
(PtcCO
2
), hemodynamics, dyspnea and comfort.
Methods
Adult CF patients who had been stabilized after requiring ventilatory support for a few days were enrolled and ventilated with HFNT and NIV for 30 min in crossover random order.
Results
Fifteen patients were enrolled. Compared to baseline, HFNT, but not NIV, reduced respiratory rate (by 3 breaths/min,
p
= 0.01) and minute ventilation (by 2 L/min,
p
= 0.01). Patients also took slightly larger tidal volumes with HFNT compared to NIV (
p
= 0.02). TFdi per breath was similar under the two techniques and did not change from baseline. MAP increased from baseline with NIV and compared to HFNT (
p
≤ 0.01). Comfort was poorer with the application of both HFNT and NIV than baseline. No differences were found for heart rate, SpO
2
, PtcCO
2
or dyspnea.
Conclusions
In adult CF patients stabilized after indication for ventilatory support, HFNT and NIV have similar effects on diaphragmatic work per breath, but high-flow therapy confers additional physiological benefits by decreasing respiratory rate and minute ventilation.
Clinical trial registration
Ethics Committee of St. Michael’s Hospital (REB #14-338) and clinicaltrial.gov (NCT02262871).
Background:
Little is known about the nature of concussion injury among university student-athletes, including concussion incidence and rates across sports, the mechanisms of injury, the type of ...activity during competition or practice, and the time to return to academics, return to sport, and symptom resolution.
Purpose:
To describe methods of the Ivy League–Big Ten Epidemiology of Concussion Study and first epidemiologic findings.
Study Design:
Descriptive epidemiology study.
Methods:
A prospective cohort study was conducted with data accrued through a surveillance system that was launched in the 2013-2014 athletic season. Surveillance continues to operate by detecting and collecting sport-related concussion (SRC) cases and non-SRC cases in addition to outcomes among university student-athletes.
Results:
A total of 1922 cases of SRC (649 women, 1004 men) among athletes from 27 sports, including varsity sports and club rugby, were enrolled during the 5 athletic seasons from 2013-2014 through 2017-2018. American football had the most cases (n = 495, 25.8%), followed by women’s rugby (n = 199, 6.2%), men’s ice hockey (n = 106, 5.5%), men's lacrosse (n = 105, 5.5%), women's soccer (n = 103, 5.4%), wrestling (n = 93, 4.8%), and men's soccer (n = 89, 4.6%), and women's ice hockey (n = 78, 4.1%). The highest overall concussion rates occurred in women’s lacrosse (1.35 concussions per 1000 athletic exposures AEs) and football (1.26 per 1000 AEs). Rates of concussion were generally higher during competition than practice and were highest during wrestling competition (4.06 per 1000 AEs) and second highest during football competition (3.68 per 1000 AEs). The median number of concussion symptoms was 7. Time to symptom resolution was longer for athletes with ≥7 symptoms versus <7 (P < .001) but did not differ across the 4 sports with rules comparable by sex and did not differ significantly between women and men (median, 8 vs 9 days, respectively). Women and men did not differ in days to return to academics, exertion activities, or competition.
Conclusion:
This multisite collaborative endeavor has produced a robust database yielding novel opportunities to better understand the epidemiology of concussion among university student-athletes participating in a variety of sports. Given the setting and number of cases, these findings add to our understanding of SRC and are the first of many that will be generated over the coming years from this large study that continues in its sixth year.
Fetal structural anomalies, which are detected by ultrasonography, have a range of genetic causes, including chromosomal aneuploidy, copy number variations (CNVs; which are detectable by chromosomal ...microarrays), and pathogenic sequence variants in developmental genes. Testing for aneuploidy and CNVs is routine during the investigation of fetal structural anomalies, but there is little information on the clinical usefulness of genome-wide next-generation sequencing in the prenatal setting. We therefore aimed to evaluate the proportion of fetuses with structural abnormalities that had identifiable variants in genes associated with developmental disorders when assessed with whole-exome sequencing (WES).
In this prospective cohort study, two groups in Birmingham and London recruited patients from 34 fetal medicine units in England and Scotland. We used whole-exome sequencing (WES) to evaluate the presence of genetic variants in developmental disorder genes (diagnostic genetic variants) in a cohort of fetuses with structural anomalies and samples from their parents, after exclusion of aneuploidy and large CNVs. Women were eligible for inclusion if they were undergoing invasive testing for identified nuchal translucency or structural anomalies in their fetus, as detected by ultrasound after 11 weeks of gestation. The partners of these women also had to consent to participate. Sequencing results were interpreted with a targeted virtual gene panel for developmental disorders that comprised 1628 genes. Genetic results related to fetal structural anomaly phenotypes were then validated and reported postnatally. The primary endpoint, which was assessed in all fetuses, was the detection of diagnostic genetic variants considered to have caused the fetal developmental anomaly.
The cohort was recruited between Oct 22, 2014, and June 29, 2017, and clinical data were collected until March 31, 2018. After exclusion of fetuses with aneuploidy and CNVs, 610 fetuses with structural anomalies and 1202 matched parental samples (analysed as 596 fetus-parental trios, including two sets of twins, and 14 fetus-parent dyads) were analysed by WES. After bioinformatic filtering and prioritisation according to allele frequency and effect on protein and inheritance pattern, 321 genetic variants (representing 255 potential diagnoses) were selected as potentially pathogenic genetic variants (diagnostic genetic variants), and these variants were reviewed by a multidisciplinary clinical review panel. A diagnostic genetic variant was identified in 52 (8·5%; 95% CI 6·4–11·0) of 610 fetuses assessed and an additional 24 (3·9%) fetuses had a variant of uncertain significance that had potential clinical usefulness. Detection of diagnostic genetic variants enabled us to distinguish between syndromic and non-syndromic fetal anomalies (eg, congenital heart disease only vs a syndrome with congenital heart disease and learning disability). Diagnostic genetic variants were present in 22 (15·4%) of 143 fetuses with multisystem anomalies (ie, more than one fetal structural anomaly), nine (11·1%) of 81 fetuses with cardiac anomalies, and ten (15·4%) of 65 fetuses with skeletal anomalies; these phenotypes were most commonly associated with diagnostic variants. However, diagnostic genetic variants were least common in fetuses with isolated increased nuchal translucency (≥4·0 mm) in the first trimester (in three 3·2% of 93 fetuses).
WES facilitates genetic diagnosis of fetal structural anomalies, which enables more accurate predictions of fetal prognosis and risk of recurrence in future pregnancies. However, the overall detection of diagnostic genetic variants in a prospectively ascertained cohort with a broad range of fetal structural anomalies is lower than that suggested by previous smaller-scale studies of fewer phenotypes. WES improved the identification of genetic disorders in fetuses with structural abnormalities; however, before clinical implementation, careful consideration should be given to case selection to maximise clinical usefulness.
UK Department of Health and Social Care and The Wellcome Trust.
Females with balanced X-autosome translocations are a clinically heterogeneous group of patients in which X breakpoint position and replication behaviour may influence phenotypic outcome. This study ...reviewed all cases reported by UK cytogenetics laboratories over a 15-year period (1983-1997). Publication bias was avoided by reviewing all reported cases. One hundred and four female carriers were identified, 62 of who were probands. By reason for referral, these were: multiple congenital abnormalities and/or developmental delay (MCA/DD): 26 (42%); gonadal dysfunction: 22 (35%); phenotypically normal with or without recurrent miscarriage (NRM): 9 (15%); recognized X-linked syndrome: 5 (8%). The information obtained was compared with published data and with data from the authors' own laboratories of female patients with balanced autosome-autosome translocations (n=115). We concluded that: (1) MCA/DD cases were significantly over-represented compared to previous published data (P<0.005) and were more common than in female probands with balanced autosome-autosome translocations (P<0.05). (2) MCA/DD cases showed random breakpoint distribution along the X chromosome (P>0.05). MCA/DD cases with subtelomeric breakpoints at Xp22 or Xq28 were not always associated with deviation from the expected pattern of X-inactivation where this was known. De novo cases were significantly more likely to be assigned as MCA/DD than any other category (P<0.005). (3) Gonadal dysfunction (GD) was invariably associated with a 'critical region' breakpoint, Xq13-q26, (20/22 probands). However, 7/44 (16%) of patients surveyed had breakpoints within Xq13-Xq26 and proven fertility. (4) Recognized 'X-linked syndrome' cases were significantly under-represented (P<0.001) compared to previous published data.
We examined whether the “friendliness” of college counseling center websites to students with lesbian, gay, bisexual, transgender, and queer, plus other identities (LGBTQ+) varied by state‐level ...structural policies on hate crime, employment nondiscrimination, and religious exemption. Results from our analyses of variance showed that website friendliness was significantly higher in states that offered hate‐crime and employment nondiscrimination protections to LGBTQ+ individuals. Our findings highlight the need to intervene at multiple ecological levels to build inclusive college communities.
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