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1.
Lancet Microbe ; 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38703782

ABSTRACT

BACKGROUND: A SARS-CoV-2 controlled human infection model (CHIM) has been successfully established in seronegative individuals using a dose of 1×101 50% tissue culture infectious dose (TCID50) pre-alpha SARS-CoV-2 virus. Given the increasing prevalence of seropositivity to SARS-CoV-2, a CHIM that could be used for vaccine development will need to induce infection in those with pre-existing immunity. Our aim was to find a dose of pre-alpha SARS-CoV-2 virus that induced infection in previously infected individuals. METHODS: Healthy, UK volunteers aged 18-30 years, with proven (quantitative RT-PCR or lateral flow antigen test) previous SARS-CoV-2 infection (with or without vaccination) were inoculated intranasally in a stepwise dose escalation CHIM with either 1×101, 1×102, 1×10³, 1×104, or 1×105 TCID50 SARS-CoV-2/human/GBR/484861/2020, the same virus used in the seronegative CHIM. Post-inoculation, volunteers were quarantined in functionally negative pressure rooms (Oxford, UK) for 14 days and until 12-hourly combined oropharyngeal-nasal swabs were negative for viable virus by focus-forming assay. Outpatient follow-up continued for 12 months post-enrolment, with additional visits for those who developed community-acquired SARS-CoV-2 infection. The primary objective was to identify a safe, well tolerated dose that induced infection (defined as two consecutive SARS-CoV-2 positive PCRs starting 24 h after inoculation) in 50% of seropositive volunteers. This study is registered with ClinicalTrials.gov (NCT04864548); enrolment and follow-up to 12 months post-enrolment are complete. FINDINGS: Recruitment commenced on May 6, 2021, with the last volunteer enrolled into the dose escalation cohort on Nov 24, 2022. 36 volunteers were enrolled, with four to eight volunteers inoculated in each dosing group from 1×101 to 1×105 TCID50 SARS-CoV-2. All volunteers have completed quarantine, with follow-up to 12 months complete. Despite dose escalation to 1×105 TCID50, we were unable to induce sustained infection in any volunteers. Five (14%) of 36 volunteers were considered to have transient infection, based on the kinetic of their PCR-positive swabs. Transiently infected volunteers had significantly lower baseline mucosal and systemic SARS-CoV-2-specific antibody titres and significantly lower peripheral IFNγ responses against a CD8+ T-cell SARS-CoV-2 peptide pool than uninfected volunteers. 14 (39%) of 36 volunteers subsequently developed breakthrough infection with the omicron variant after discharge from quarantine. Most adverse events reported by volunteers in quarantine were mild, with fatigue (16 [44%]) and stuffy nose (16 [44%]) being the most common. There were no serious adverse events. INTERPRETATION: Our study demonstrates potent protective immunity induced by homologous vaccination and homologous or heterologous previous SARS-CoV-2 infection. The community breakthrough infections seen with the omicron variant supports the use of newer variants to establish a model with sufficient rate of infection for use in vaccine and therapeutic development. FUNDING: Wellcome Trust and Department for Health and Social Care.

2.
Lancet Infect Dis ; 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38621405

ABSTRACT

BACKGROUND: Mycobacterium tuberculosis is the main causative agent of tuberculosis. BCG, the only licensed vaccine, provides inadequate protection against pulmonary tuberculosis. Controlled human infection models are useful tools for vaccine development. We aimed to determine a safe dose of aerosol-inhaled live-attenuated Mycobacterium bovis BCG as a surrogate for M tuberculosis infection, then compare the safety and tolerability of infection models established using aerosol-inhaled and intradermally administered BCG. METHODS: This phase 1 controlled human infection trial was conducted at two clinical research facilities in the UK. Healthy, immunocompetent adults aged 18-50 years, who were both M tuberculosis-naive and BCG-naive and had no history of asthma or other respiratory diseases, were eligible for the trial. Participants were initially enrolled into group 1 (receiving the BCG Danish strain); the trial was subsequently paused because of a worldwide shortage of BCG Danish and, after protocol amendment, was restarted using the BCG Bulgaria strain (group 2). After a dose-escalation study, during which participants were sequentially allocated to receive either 1 × 103, 1 × 104, 1 × 105, 1 × 106, or 1 × 107 colony-forming units (CFU) of aerosol BCG, the maximum tolerated dose was selected for the randomised controlled trial. Participants in this trial were randomly assigned (9:12), by variable block randomisation and using sequentially numbered sealed envelopes, to receive aerosol BCG (1 × 107 CFU) and intradermal saline or intradermal BCG (1 × 106 CFU) and aerosol saline. Participants were masked to treatment allocation until day 14. The primary outcome was to compare the safety of a controlled human infection model based on aerosol-inhaled BCG versus one based on intradermally administered BCG, and the secondary outcome was to evaluate BCG recovery in the airways of participants who received aerosol BCG or skin biopsies of participants who received intradermal BCG. BCG was detected by culture and by PCR. The trial is registered at ClinicalTrials.gov, NCT02709278, and is complete. FINDINGS: Participants were assessed for eligibility between April 7, 2016, and Sept 29, 2018. For group 1, 15 participants were screened, of whom 13 were enrolled and ten completed the study; for group 2, 60 were screened and 33 enrolled, all of whom completed the study. Doses up to 1 × 107 CFU aerosol-inhaled BCG were sufficiently well tolerated. No significant difference was observed in the frequency of adverse events between aerosol and intradermal groups (median percentage of solicited adverse events per participant, post-aerosol vs post-intradermal BCG: systemic 7% [IQR 2-11] vs 4% [1-13], p=0·62; respiratory 7% [1-19] vs 4% [1-9], p=0·56). More severe systemic adverse events occurred in the 2 weeks after aerosol BCG (15 [12%] of 122 reported systemic adverse events) than after intradermal BCG (one [1%] of 94; difference 11% [95% CI 5-17]; p=0·0013), but no difference was observed in the severity of respiratory adverse events (two [1%] of 144 vs zero [0%] of 97; 1% [-1 to 3]; p=0·52). All adverse events after aerosol BCG resolved spontaneously. One serious adverse event was reported-a participant in group 2 was admitted to hospital to receive analgesia for a pre-existing ovarian cyst, which was deemed unrelated to BCG infection. On day 14, BCG was cultured from bronchoalveolar lavage samples after aerosol infection and from skin biopsy samples after intradermal infection. INTERPRETATION: This first-in-human aerosol BCG controlled human infection model was sufficiently well tolerated. Further work will evaluate the utility of this model in assessing vaccine efficacy and identifying potential correlates of protection. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, National Institute for Health Research Oxford Biomedical Research Centre, Thames Valley Clinical Research Network, and TBVAC2020.

3.
Front Psychiatry ; 14: 1279255, 2023.
Article in English | MEDLINE | ID: mdl-38094593

ABSTRACT

Introduction: Moral injury, predominantly studied in military populations, has garnered increased attention in the healthcare setting, in large part due to the psychological and emotional consequences of the COVID-19 pandemic. The measurement of moral injury with instrumentation adapted from military settings and validated by frontline healthcare personnel is essential to assess prevalence and guide intervention. This study aimed to validate the Moral Injury Outcome Scale (MIOS) in the population of acute care. Methods: A sample of 309 acute care nurses completed surveys regarding moral injury, depression, anxiety, burnout, professional fulfillment, spiritual wellbeing, and post-traumatic stress disorder symptoms. Confirmatory factor analysis was conducted as well as an assessment of reliability and validity. Results: The internal consistency of the 14-item MIOS was 0.89. The scale demonstrated significant convergent and discriminant validity, and the test of construct validity confirmed the two-factor structure of shame and trust violations in this clinical population. Regression analysis indicated age, race, and marital status-related differences in the experience of moral injury. Discussion: The MIOS is valid and reliable in acute care nursing populations and demonstrates sound psychometric properties. Scores among nurses diverge from those of military personnel in areas that may inform distinctions in interventions to address moral injury in these populations.

4.
J Health Care Chaplain ; : 1-19, 2023 Oct 19.
Article in English | MEDLINE | ID: mdl-37853721

ABSTRACT

Hospital-based chaplains provide crucial spiritual and emotional care to patients, families, and staff during times of intense life changes and crises. Chaplains are regularly exposed to suffering and their work may result in personal mental and emotional health challenges. To understand chaplains' perceptions of the impact of their work and methods to cope, a secondary analysis of a mixed-methods study on chaplain well-being was undertaken. Qualitative interviews were conducted with nine hospital-based chaplains and data were coded and analyzed using thematic analysis. Results revealed that participants perceive their work as offering both trials and rewards, and their efforts to cope with trials include interpersonal support, intrapersonal resources, and spiritual resilience. Personal insights into chaplains' experiences may help inform organizational interventions to support these essential members of the care team.

5.
J Genet Couns ; 2023 Aug 02.
Article in English | MEDLINE | ID: mdl-37533143

ABSTRACT

Preimplantation genetic testing for monogenic disorders (PGT-M) is a reproductive technology used in conjunction with in-vitro fertilization (IVF) to reduce the risk of passing on a known genetic condition from parent to child. There is limited research describing the experience and emotional impact of PGT-M among individuals with inherited aortic or vascular disease (IAVD). Our qualitative study aims to explore the factors that influence reproductive decision-making and the uptake of PGT-M within this population. Individuals diagnosed with IAVD who have considered PGT-M, and/or their reproductive partner, were recruited using internal clinical databases and advocacy organizations. Virtual semi-structured interviews were conducted using an interview guide that included questions related to participants' lived experience of their condition, risk perception, reproductive history, familiarity with PGT-M/IVF, and financial/psychosocial considerations. A total of 17 interviews were completed (13 affected individuals, 4 unaffected partners) and analyzed using thematic analysis. Emergent themes included: (1) the lived experience and perceived severity of disease; (2) need for comprehensive, balanced, and timely information; (3) and impact of personal values and circumstances. When discussing the impact of lived experience on reproductive decision-making, participants identified the physical and emotional impact of disease and variability of disease as factors influencing the uptake of PGT-M. Many described PGT-M as the only reproductive option presented to them by providers. Even so, participants expressed gaps in their understanding of PGT-M, particularly regarding cost/insurance coverage and the experience of IVF. Finally, participants recognized that the decision to pursue PGT-M primarily requires introspection and evaluation of one's values, but that cost remains a significant consideration. The findings from our study highlight the complexity of reproductive decision-making for individuals with IAVD and provide insight into their psychological and informational needs when engaging in this process. Providers can use these findings to tailor their discussions about reproductive decision-making with this patient cohort.

6.
Front Vet Sci ; 10: 1146091, 2023.
Article in English | MEDLINE | ID: mdl-37187927

ABSTRACT

A 4-year-old neutered-male Australian Shepherd was presented to an emergency and referral hospital for an acute onset of neurologic signs and abnormal mentation. Seven days prior, the patient had been diagnosed with hypoadrenocorticism and was treated accordingly at another hospital. Based on recent clinical history, the neurologic signs were consistent with thalamic and brainstem deficits and suspected to be caused by osmotic demyelination syndrome secondary to rapid correction of hyponatremia. A brain MRI confirmed lesions consistent with osmotic demyelination syndrome. The patient's clinical signs initially worsened, and he required intensive nursing care with multimodal sedation, close monitoring of electrolytes and tailored fluid therapy. The patient recovered and was discharged on day seven of hospitalization. Four and a half months later, re-evaluation of the patient showed complete resolution of the neurological deficits with a now unremarkable neurological exam, and follow-up MRI revealed still present, yet improved bilateral thalamic lesions. This is the first known veterinary case report of sequential brain imaging of a dog that has recovered from osmotic demyelination syndrome. In humans, patients can have evidence of near to full clinical recovery, yet imaging findings may still be abnormal several months after recovery. This report details similar imaging findings in a canine with improved clinical signs, despite persistent lesions on brain MRI. Prognosis of canines with osmotic demyelination syndrome may be better than previously perceived, despite the severity of clinical signs and brain lesions apparent on MRI.

8.
J Pastoral Care Counsel ; 77(2): 101-112, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36591899

ABSTRACT

This mixed-methods pilot study explored the psychological and emotional experiences of chaplains and the feasibility, acceptability, and impact of workshops designed to support chaplain well-being. After the workshops, scores on a measure of self-compassion increased, while secondary traumatic stress and burnout scores decreased. Qualitative data reflected the range of experiences of chaplaincy as well as the benefits of the workshops. This pilot study supports further exploration of organizational interventions to promote chaplain well-being.


Subject(s)
Burnout, Professional , Pastoral Care , Humans , Clergy/psychology , Pilot Projects , Delivery of Health Care
9.
Nat Commun ; 13(1): 6594, 2022 11 03.
Article in English | MEDLINE | ID: mdl-36329009

ABSTRACT

Tuberculosis vaccine development is hindered by the lack of validated immune correlates of protection. Exploring immune correlates of risk of disease and/or infection in prospective samples can inform this field. We investigate whether previously identified immune correlates of risk of TB disease also associate with increased risk of M.tb infection in BCG-vaccinated South African infants, who became infected with M.tb during 2-3 years of follow-up. M.tb infection is defined by conversion to positive reactivity in the QuantiFERON test. We demonstrate that inflammation and immune activation are associated with risk of M.tb infection. Ag85A-specific IgG is elevated in infants that were subsequently infected with M.tb, and this is coupled with upregulated gene expression of immunoglobulin-associated genes and type-I interferon. Plasma levels of IFN-[Formula: see text]2, TNF-[Formula: see text], CXCL10 (IP-10) and complement C2 are also higher in infants that were subsequently infected with M.tb.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Infant , Humans , BCG Vaccine , Antigens, Bacterial , Prospective Studies , Interferon-gamma , Tuberculosis/microbiology , Inflammation , Mycobacterium tuberculosis/genetics
11.
Nat Commun ; 13(1): 5106, 2022 08 30.
Article in English | MEDLINE | ID: mdl-36042188

ABSTRACT

Accurate and efficient classification of variant pathogenicity is critical for research and clinical care. Using data from three large studies, we demonstrate that population-based associations between rare variants and quantitative endophenotypes for three monogenic diseases (low-density-lipoprotein cholesterol for familial hypercholesterolemia, electrocardiographic QTc interval for long QT syndrome, and glycosylated hemoglobin for maturity-onset diabetes of the young) provide evidence for variant pathogenicity. Effect sizes are associated with pathogenic ClinVar assertions (P < 0.001 for each trait) and discriminate pathogenic from non-pathogenic variants (area under the curve 0.82-0.84 across endophenotypes). An effect size threshold of ≥ 0.5 times the endophenotype standard deviation nominates up to 35% of rare variants of uncertain significance or not in ClinVar in disease susceptibility genes with pathogenic potential. We propose that variant associations with quantitative endophenotypes for monogenic diseases can provide evidence supporting pathogenicity.


Subject(s)
Endophenotypes , Long QT Syndrome , Disease Susceptibility , Humans , Virulence
12.
Front Vet Sci ; 9: 938021, 2022.
Article in English | MEDLINE | ID: mdl-35903141

ABSTRACT

A 4-year-old, female-spayed, mixed breed dog, weighing 24.2 kg, was presented for acute ingestion of ~12.3 mg/kg of Adderall XRⓇ, an extended-release amphetamine medication. In dogs, the oral median lethal dose for amphetamines ranges anywhere from 9-11 mg/kg to 20-27 mg/kg. On presentation, the patient was agitated, tachycardic and hypertensive. Initial treatment was instituted with intravenous lipid emulsion (IVLE) therapy, and baseline and post-treatment amphetamine concentrations were quantified in serum and plasma. In both serum and plasma, post-IVLE concentrations of amphetamine were lower 1 h after treatment and IVLE was the only treatment instituted during this time. The dog improved significantly while in hospital and was discharged <24 h after presentation. This is the first known reported use of IVLE for treatment of amphetamine toxicosis with documented decreases in both serum and plasma amphetamine levels shortly after administration of IVLE.

13.
J Genet Couns ; 31(6): 1290-1305, 2022 12.
Article in English | MEDLINE | ID: mdl-35799446

ABSTRACT

Genetic testing and genetic counseling are routinely indicated for patients with hypertrophic cardiomyopathy (HCM); however, the uptake and utility of these services is not entirely understood. This systematic review and meta-analysis summarizes the uptake and utility of genetic counseling and genetic testing for patients with HCM and their at-risk family members, as well as the impact of genetic counseling/testing on patient-reported outcomes (PROs). A systematic search was performed through March 12, 2021. Meta-analyses were performed whenever possible; other findings were qualitatively summarized. Forty-eight studies met inclusion criteria (47 observational, 1 randomized). Uptake of genetic testing in probands was 57% (95% confidence interval [CI]: 40, 73). Uptake of cascade screening for at-risk relatives were as follows: 61% for cascade genetic testing (95% CI: 45, 75), 58% for cardiac screening (e.g. echocardiography) (95% CI: 40, 73), and 69% for either/both approaches (95% CI: 43, 87). In addition, relatives of probands with a positive genetic test result were significantly more likely to undergo cascade screening compared to relatives of probands with a negative result (odds ratio = 3.17, 95% CI: 2.12, 4.76). Overall, uptake of genetic counseling in both probands and relatives ranged from 37% to 84%. Multiple studies found little difference in PROs between individuals receiving positive versus negative genetic test results; however, other studies found that individuals with positive genetic test results experienced worse psychological outcomes. Genetic testing may also inform life choices, particularly decisions related to reproduction and insurance. Genetic counseling was associated with high satisfaction, increased perceived personal control and empowerment, and decreased anxiety. Approximately half to three-quarters of patients with HCM and their relatives undergo genetic testing or cascade screening. PROs after genetic testing varied and genetic counseling was associated with high satisfaction and improved PROs.


Subject(s)
Cardiomyopathy, Hypertrophic , Genetic Counseling , Humans , Genetic Testing/methods , Cardiomyopathy, Hypertrophic/diagnosis , Cardiomyopathy, Hypertrophic/genetics , Cardiomyopathy, Hypertrophic/psychology , Family , Echocardiography
14.
Environ Pollut ; 308: 119619, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-35709917

ABSTRACT

Mercury (Hg) is a toxic trace element widely distributed in the environment, which particularly accumulates in top predators, including seabirds. Among seabirds, large gulls (Larus sp) are generalist feeders, foraging in both terrestrial and marine habitats, making them relevant bioindicators of local coastal Hg contamination. In the present study, we reported blood Hg concentrations in adults and chicks of four different gull species breeding on the French Atlantic coast: the European herring gull (Larus argentatus), the Lesser black-backed gull (L. fuscus), the Great black-backed gull (L. marinus) and the Yellow-legged gull (L. michahellis). We also investigated the potential role of foraging ecology in shaping Hg contamination across species, using the unique combination of three dietary tracers (carbon, nitrogen and sulfur stable isotopes) and biologging (GPS tracking). A high concentration of Hg was associated with high trophic position and a marine diet in gulls, which was corroborated by birds' space use strategy during foraging trips. Adults of all four species reached Hg concentrations above reported toxicity thresholds. Specifically, adults of Great black-backed gulls had a high trophic marine specialized diet and significantly higher Hg concentrations than the three other species. Blood Hg was 4-7 times higher in adults than in chicks, although chicks of all species received mainly marine and high trophic position prey, which is expected to be the cause of blood Hg concentrations of toxic concern. By using both stable isotopes and GPS tracking, the present study provides compelling insights on the main feeding habits driving Hg contamination in a seabird assemblage feeding in complex coastal environments.


Subject(s)
Charadriiformes , Mercury , Animals , Ecosystem , Environmental Monitoring , Isotopes , Mercury/analysis
15.
J Genet Couns ; 31(6): 1273-1281, 2022 12.
Article in English | MEDLINE | ID: mdl-35763674

ABSTRACT

First-degree relatives of a proband with an inherited cardiac condition (ICC) are offered predictive genetic testing for the pathogenic or likely pathogenic (P/LP) cardiac gene variant (CGV) to clarify their risk for the familial condition. Relatives who test negative for a familial P/LP CGV typically do not require longitudinal cardiac surveillance. To our knowledge, no previous study has investigated adjustment to risk reduction and subsequent screening practices in genotype-negative relatives from an ICC population. We thus investigated risk perception and ongoing screening practices in genotype-negative adults who received cardiac genetic counseling. Correlations between clinical and demographic variables and risk perception and screening practices were also investigated. On average, participants (n = 71) reported a perceived 19.5% lifetime risk of developing the ICC in their family, despite their negative genetic test result. The majority (54%) of participants reported having undergone cardiac screening after disclosure of their negative result. There were no significant correlations between clinical and demographic variables and risk perception or screening practices. Furthermore, risk perception was not found to impact the likelihood of cardiac screening. These findings suggest that even with comprehensive cardiac genetic counseling, a proportion of this population did not accurately comprehend or recall their cardiac disease risk. Additional interventions beyond traditional result disclosure should be explored to help genotype-negative individuals adjust to their reduction in risk for a familial ICC.


Subject(s)
Genetic Testing , Heart Diseases , Adult , Humans , Genetic Counseling , Family/psychology , Disclosure
16.
Sci Rep ; 12(1): 7808, 2022 05 12.
Article in English | MEDLINE | ID: mdl-35552463

ABSTRACT

Bacille Calmette-Guérin (BCG), the only currently licenced tuberculosis vaccine, may exert beneficial non-specific effects (NSE) in reducing infant mortality. We conducted a randomised controlled clinical study in healthy UK adults to evaluate potential NSE using functional in-vitro growth inhibition assays (GIAs) as a surrogate of protection from four bacteria implicated in infant mortality. Volunteers were randomised to receive BCG intradermally (n = 27) or to be unvaccinated (n = 8) and were followed up for 84 days; laboratory staff were blinded until completion of the final visit. Using GIAs based on peripheral blood mononuclear cells, we observed a significant reduction in the growth of the Gram-negative bacteria Escherichia coli and Klebsiella pneumonia following BCG vaccination, but no effect for the Gram-positive bacteria Staphylococcus aureus and Streptococcus agalactiae. There was a modest association between S. aureus nasal carriage and growth of S. aureus in the GIA. Our findings support a causal link between BCG vaccination and improved ability to control growth of heterologous bacteria. Unbiased assays such as GIAs are potentially useful tools for the assessment of non-specific as well as specific effects of TB vaccines. This study was funded by the Bill and Melinda Gates Foundation and registered with ClinicalTrials.gov (NCT02380508, 05/03/2015; completed).


Subject(s)
BCG Vaccine , Tuberculosis Vaccines , Adult , Humans , Infant , Leukocytes, Mononuclear , Staphylococcus aureus , Vaccination
17.
Circulation ; 145(20): 1524-1533, 2022 05 17.
Article in English | MEDLINE | ID: mdl-35389749

ABSTRACT

BACKGROUND: Rare sequence variation in genes underlying cardiac repolarization and common polygenic variation influence QT interval duration. However, current clinical genetic testing of individuals with unexplained QT prolongation is restricted to examination of monogenic rare variants. The recent emergence of large-scale biorepositories with sequence data enables examination of the joint contribution of rare and common variations to the QT interval in the population. METHODS: We performed a genome-wide association study of the QTc in 84 630 UK Biobank participants and created a polygenic risk score (PRS). Among 26 976 participants with whole-genome sequencing and ECG data in the TOPMed (Trans-Omics for Precision Medicine) program, we identified 160 carriers of putative pathogenic rare variants in 10 genes known to be associated with the QT interval. We examined QTc associations with the PRS and with rare variants in TOPMed. RESULTS: Fifty-four independent loci were identified by genome-wide association study in the UK Biobank. Twenty-one loci were novel, of which 12 were replicated in TOPMed. The PRS composed of 1 110 494 common variants was significantly associated with the QTc in TOPMed (ΔQTc/decile of PRS=1.4 ms [95% CI, 1.3 to 1.5]; P=1.1×10-196). Carriers of putative pathogenic rare variants had longer QTc than noncarriers (ΔQTc=10.9 ms [95% CI, 7.4 to 14.4]). Of individuals with QTc>480 ms, 23.7% carried either a monogenic rare variant or had a PRS in the top decile (3.4% monogenic, 21% top decile of PRS). CONCLUSIONS: QTc duration in the population is influenced by both rare variants in genes underlying cardiac repolarization and polygenic risk, with a sizeable contribution from polygenic risk. Comprehensive assessment of the genetic determinants of QTc prolongation includes incorporation of both polygenic and monogenic risk.


Subject(s)
Genome-Wide Association Study , Long QT Syndrome , Electrocardiography , Heterozygote , Humans , Long QT Syndrome/diagnosis , Long QT Syndrome/genetics , Multifactorial Inheritance , Whole Genome Sequencing
18.
Open Heart ; 9(1)2022 04.
Article in English | MEDLINE | ID: mdl-35387861

ABSTRACT

OBJECTIVE: This study summarises the diagnostic validity and clinical utility of genetic testing for patients with hypertrophic cardiomyopathy (HCM) and their at-risk relatives. METHODS: A systematic search was performed in PubMed (MEDLINE), Embase, CINAHL and Cochrane Central Library databases from inception through 2 March 2020. Subgroup and sensitivity analyses were prespecified for individual sarcomere genes, presence/absence of pathogenic variants, paediatric and adult cohorts, family history, inclusion of probands, and variant classification method. Study quality was assessed using the Newcastle-Ottawa tool. RESULTS: A total of 132 articles met inclusion criteria. The detection rate based on pathogenic and likely pathogenic variants was significantly higher in paediatric cohorts compared with adults (56% vs 42%; p=0.01) and in adults with a family history compared with sporadic cases (59% vs 33%; p=0.005). When studies applied current, improved, variant interpretation standards, the adult detection rate significantly decreased from 42% to 33% (p=0.0001) because less variants met criteria to be considered pathogenic. The mean difference in age-of-onset in adults was significantly earlier for genotype-positive versus genotype-negative cohorts (8.3 years; p<0.0001), MYH7 versus MYBPC3 cohorts (8.2 years; p<0.0001) and individuals with multiple versus single variants (7.0 years; p<0.0002). Overall, disease penetrance in adult cohorts was 62%, but differed significantly depending on if probands were included or excluded (73% vs 55%; p=0.003). CONCLUSIONS: This systematic review and meta-analysis is the first, to our knowledge, to collectively quantify historical understandings of detection rate, genotype-phenotype associations and disease penetrance for HCM, while providing the answers to important routine clinical questions and highlighting key areas for future study.


Subject(s)
Cardiomyopathy, Hypertrophic , Cardiomyopathy, Hypertrophic/diagnosis , Cardiomyopathy, Hypertrophic/genetics , Child , Genetic Association Studies , Genetic Testing , Genotype , Humans , Penetrance
19.
Nurse Lead ; 20(2): 188-192, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35280339

ABSTRACT

Health care organizations are facing the fallout from inadequate nurse staffing in addition to the emotional and spiritual tolls of the COVID-19 pandemic. Organizations must strategically differentiate themselves by novel methods of recruitment and retention, including care of the nurse as a whole person. Tactical strategies can be implemented by nurse leaders to promote the spiritual well-being of the nursing workforce. These strategies include incorporating spirituality and soft skills into nursing orientation, developing and providing interventions to support spiritual well-being, and implementing methods to provide spiritual care of patients by nurses.

20.
Med Sci Educ ; 32(1): 9-11, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35186427

ABSTRACT

Nutritional status greatly affects the health of patients, yet the time devoted to nutrition curriculum in medical school is minimal. We implemented a novel approach of teaching the Nutrition Focused Physical Exam (NFPE) as a tool to demonstrate the importance of assessing the nutritional status of patients and learning about malnutrition and nutrient deficiencies.

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