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Sodium-glucose cotransporter-2 inhibitors reduce cardiovascular outcomes in patients with congestive heart failure and a biventricular circulation. Congestive heart failure in Fontan univentricular circulation is distinctly different. Experience with sodium-glucose cotransporter-2 inhibitors in this group has not yet been well described.
Objectives:
This work describes safety and tolerability of sodium-glucose cotransporter-2 inhibitors in patients with Fontan circulation.
Methods:
Single-centre review of patients with Fontan circulation prescribed a sodium-glucose cotransporter-2 inhibitors for congestive heart failure. Primary outcome was tolerability or need for discontinuation. Secondary outcomes were changes in New York Heart Association class, congestive heart failure hospitalisation, ventricular function, exercise performance, and laboratory values.
Results:
We identified 25 patients with Fontan circulation prescribed an sodium-glucose cotransporter-2 inhibitors, most with a systemic right ventricle. Over a third of subjects had at least moderately reduced baseline ventricular function. Baseline catheterisation showed a mean Fontan pressure of 17.1 ± 3.7 mmHg and pulmonary capillary wedge pressure 11.7 ± 3.2 mmHg at rest; 59% had occult diastolic dysfunction with abnormal pulmonary capillary wedge pressure elevation following volume expansion. Most were on congestive heart failure medications and/or a pulmonary vasodilator prior to sodium-glucose cotransporter-2 inhibitors addition, and three had a congestive heart failure hospitalisation within the previous year. All reported good medication tolerance except one patient was nonadherent to medications and two discontinued sodium-glucose cotransporter-2 inhibitors for perceived side effects. There were no significant differences in secondary outcomes. There was, however, a downward trend of serum brain natriuretic peptide (n = 13) and improved peak VO2 (n = 6), though neither statistically significant (p > 0.05).
Conclusion:
This series, the largest published to date, suggests that sodium-glucose cotransporter-2 inhibitors are safe and tolerable congestive heart failure therapy in Fontan circulation. Further research is warranted to explore therapy in this unique population.
Background: Sellar and suprasellar pediatric lesions are uncommon. Endoscopic transnasal transphenoidal surgery (ETTS) is the preferred treatment, but early post-op MRI is hindered by sphenoidal packing. This study aims to assess iMRI safety and efficacy in pediatric ETTS cases. Methods: We performed a retrospective review from Jan 01, 2015 to Dec 31, 2022, evaluating use of iMRI. We determined if the goals of the surgery (biopsy, cyst decompression, subtotal resection, gross total resection) were met, and iMRI’s influence on surgery outcomes. We examined patient age, surgery duration, length of stay, histopathology results, surgical complications, post-op MRIs within 1 month, and tumor progression/recurrence. Results: Over eight years, 20 pediatric ETTS procedures, 14 with iMRI, were conducted. Achieving goals in 13 cases, iMRI prompted extra surgery once. Two adenomas progressed, requiring a second surgery, and craniopharyngioma cases had complications, needing further interventions. Hospital stays varied (1-9 days), with a mean surgery duration of 6 hours and 47 minutes. The study underscores iMRI’s potential impact, stressing the necessity for more research in pediatric transsphenoidal surgeries. Conclusions: While intraoperative MRI in pediatric transsphenoidal surgeries may aid goal verification, this small study doesn’t conclusively demonstrate improved outcomes. Complication rates align with non-IMRI procedures, highlighting the need for further research.
The Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (‘P-POSSUM’) is a two-part scoring system that includes a physiological assessment and a measure of operative severity. This study sought to determine whether risk estimates for this scoring system could be used in major head and neck reconstructive surgery.
Method
A retrospective review was performed of patients undergoing resection for a temporal bone malignancy in a single head and neck centre in Dublin, Ireland, from 2002 to 2021.
Results
The mean ± standard deviation morbidity estimate calculated using the scoring system was 47.6 per cent ± 19.5 per cent. The actual rate of complications was 47 per cent. The optimal cut-off for the scoring system was calculated using the Youden index from the receiver operating characteristic curve, which was 40.5 per cent in this case.
Conclusion
The study indicates that the Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity is a useful tool for predicting morbidity risk in patients undergoing head and neck resection with reconstruction for temporal bone malignancies.
To identify the impact of universal masking on COVID-19 incidence and putative SARS-CoV-2 transmissions events among children’s hospital healthcare workers (HCWs).
Design:
Quasi-experimental study.
Setting:
Single academic free-standing children’s hospital.
Methods:
We performed whole-genome sequencing of SARS-CoV-2- PCR-positive samples collected from HCWs 3 weeks before and 6 weeks after implementing a universal masking policy. Phylogenetic analyses were performed to identify clusters of clonally related SARS-CoV-2 indicative of putative transmission events. We measured COVID-19 incidence, SARS-CoV-2 test positivity rates, and frequency of putative transmission events before and after the masking policy was implemented.
Results:
HCW COVID-19 incidence and test positivity declined from 14.3 to 4.3 cases per week, and from 18.4% to 9.0%, respectively. Putative transmission events were only identified prior to universal masking.
Conclusions:
A universal masking policy was associated with reductions in HCW COVID-19 infections and occupational acquisition of SARS-CoV-2.
Substance use disorders are highly prevalent, affecting millions of Americans directly (social, occupational, and health problems) and indirectly (billions of dollars in health care costs and lost revenues due to disability). This section briefly introduces the chemical classification and neurobehavioral properties of the most commonly misused substances.
The role of the Eurasian badger (Meles meles) as a wildlife host has complicated the management of bovine tuberculosis (bTB) in cattle. Badger ranging behaviour has previously been found to be altered by culling of badgers and has been suggested to increase the transmission of bTB either among badgers or between badgers and cattle. In 2014, a five-year bTB intervention research project in a 100 km2 area in Northern Ireland was initiated involving selective removal of dual path platform (DPP) VetTB (immunoassay) test positive badgers and vaccination followed by release of DPP test negative badgers (‘Test and Vaccinate or Remove’). Home range sizes, based on position data obtained from global positioning system collared badgers, were compared between the first year of the project, where no DPP test positive badgers were removed, and follow-up years 2–4 when DPP test positive badgers were removed. A total of 105 individual badgers were followed over 21 200 collar tracking nights. Using multivariable analyses, neither annual nor monthly home ranges differed significantly in size between years, suggesting they were not significantly altered by the bTB intervention that was applied in the study area.
Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials.
Methods:
We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design.
Results:
Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field.
Conclusions:
Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.
To characterize adults with comorbid attention-deficit/hyperactivity-disorder (ADHD) and borderline personality disorder (BPD) with regard to ADHD symptoms, psychopathology, cognitive functioning and psychosocial factors.
Method
A between-group design compared a group of individuals diagnosed with ADHD (n = 40) with a group diagnosed with BPD and who also met the criteria for ADHD (ADHD + BPD) (n = 20).
Results
Significant differences were observed for both childhood and current impulsivity symptoms, whereby ADHD + BPD exhibited increased impulsivity; no differences on self-report and cognitive measures of impulsivity were reported. The ADHD + BPD group scored significantly higher on measures of depression, anxiety and numerous other axis I and II conditions. The ADHD + BPD group scored significantly lower on most measures of intellectual functioning and attention, however largely not on those relating to response inhibition. Furthermore, group differences were observed for psychosocial factors, including education, substance use and criminal record.
Conclusion
Comorbid ADHD and BPD is characterized by more symptoms of impulsivity, additional psychopathology, comparatively lower intellectual and attentional functioning and increased psychosocial difficulties.
Lamb live weight is one of the key drivers of profitability on sheep farms. Previous studies in Ireland have estimated genetic parameters for live weight and carcass composition traits using a multi-breed population rather than on an individual breed basis. The objective of the present study was to undertake genetic analyses of three lamb live weight and two carcass composition traits pertaining to purebred Texel, Suffolk and Charollais lambs born in the Republic of Ireland between 2010 and 2017, inclusive. Traits (with lamb age range in parenthesis) considered in the analyses were: pre-weaning weight (20 to 65 days), weaning weight (66 to 120 days), post-weaning weight (121 to 180 days), muscle depth (121 to 180 days) and fat depth (121 to 180 days). After data edits, 137 402 records from 50 372 lambs across 416 flocks were analysed. Variance components were derived using animal linear mixed models separately for each breed. Fixed effects included for all traits were contemporary group, age at first lambing of the dam, parity of the dam, a gender by age of the lamb interaction and a birth type by rearing type of the lamb interaction. Random effects investigated in the pre-weaning and weaning weight analyses included animal direct additive genetic, dam maternal genetic, litter common environment, dam permanent environment and residual variances. The model of analysis for post-weaning, muscle and fat depth included an animal direct additive genetic and litter common environment effect only. Significant direct additive genetic variation existed in all cases. Direct heritability for pre-weaning weight ranged from 0.14 to 0.30 across the three breeds. Weaning weight had a direct heritability ranging from 0.17 to 0.27 and post-weaning weight had a direct heritability ranging from 0.15 to 0.27. Muscle and fat depth heritability estimates ranged from 0.21 to 0.31 and 0.15 to 0.20, respectively. Positive direct correlations were evident for all traits. Results revealed ample genetic variation among animals for the studied traits and significant differences between breeds to suggest that genetic evaluations could be conducted on a per-breed basis.
To describe public health nurses’ (PHN) experiences of referring to, and families’ experiences of being referred to, a multicomponent, community-based, childhood weight management programme and to provide insight into families’ motivation to participate in and complete treatment.
Design
Qualitative study using semi-structured interviews and the draw-and-write technique.
Setting
Two geographical regions in the south and west of Ireland.
Participants
Nine PHN involved in the referral process, as well as ten parents and nine children who were referred to and completed the programme, participated in the present study.
Results
PHN were afraid of misclassifying children as obese and of approaching the subject of excess weight with parents. Peer support from other PHN as well as training in how best to talk about weight with parents were potential strategies suggested to alleviate these fears. Parents recalled the anxiety provoked by the ‘medical terminology’ used during referral and their difficulty interpreting what it meant for the health of their child. Despite initial fears, concern for their children’s future health was a major driver behind their participation. Children’s enjoyment, the social support experienced by parents as well as staff enthusiasm were key to programme completion.
Conclusions
The present study identifies the difficulties of referring families to community weight management programmes and provides practical suggestions on how to support practitioners in making referrals. It also identifies key positive factors influencing parents’ decisions to enrol in community weight management programmes. These should be maximised by staff and policy makers when developing similar programmes.
Families of children born with CHD face added stress owing to uncertainty about the magnitude of the financial burden for medical costs they will face. This study seeks to assess the family responsibility for healthcare bills during the first 12 months of life for commercially insured children undergoing surgery for severe CHD.
Methods
The MarketScan® database from Truven was used to identify commercially insured infants in 39 states from 2010 to 2012 with an ICD-9 diagnosis code for transposition of the great arteries, tetralogy of Fallot, or truncus arteriosus, as well as the corresponding procedure code for complete repair. Data extraction identified payment responsibilities of the patients’ families in the form of co-payments, deductibles, and co-insurance during the 1st year of life.
Results
There were 481 infants identified who met the criteria. Average family responsibility for healthcare bills during the 1st year of life was $2928, with no difference between the three groups. The range of out-of-pocket costs was $50–$18,167. Initial hospitalisation and outpatient care accounted for the majority of these responsibilities.
Conclusions
Families of commercially insured children with severe CHD requiring corrective surgery face an average of ~$3000 in out-of-pocket costs for healthcare bills during the first 12 months of their child’s life, although the amount varied considerably. This information provides a framework to alleviate some of the uncertainty surrounding healthcare financial responsibilities, and further examination of the origination of these expenditures may be useful in informing future healthcare policy discussion.
Early detection of karyotype abnormalities, including aneuploidy, could aid producers in identifying animals which, for example, would not be suitable candidate parents. Genome-wide genetic marker data in the form of single nucleotide polymorphisms (SNPs) are now being routinely generated on animals. The objective of the present study was to describe the statistics that could be generated from the allele intensity values from such SNP data to diagnose karyotype abnormalities; of particular interest was whether detection of aneuploidy was possible with both commonly used genotyping platforms in agricultural species, namely the Applied BiosystemsTM AxiomTM and the Illumina platform. The hypothesis was tested using a case study of a set of dizygotic X-chromosome monosomy 53,X sheep twins. Genome-wide SNP data were available from the Illumina platform (11 082 autosomal and 191 X-chromosome SNPs) on 1848 male and 8954 female sheep and available from the AxiomTM platform (11 128 autosomal and 68 X-chromosome SNPs) on 383 female sheep. Genotype allele intensity values, either as their original raw values or transformed to logarithm intensity ratio (LRR), were used to accurately diagnose two dizygotic (i.e. fraternal) twin 53,X sheep, both of which received their single X chromosome from their sire. This is the first reported case of 53,X dizygotic twins in any species. Relative to the X-chromosome SNP genotype mean allele intensity values of normal females, the mean allele intensity value of SNP genotypes on the X chromosome of the two females monosomic for the X chromosome was 7.45 to 12.4 standard deviations less, and were easily detectable using either the AxiomTM or Illumina genotype platform; the next lowest mean allele intensity value of a female was 4.71 or 3.3 standard deviations less than the population mean depending on the platform used. Both 53,X females could also be detected based on the genotype LRR although this was more easily detectable when comparing the mean LRR of the X chromosome of each female to the mean LRR of their respective autosomes. On autopsy, the ovaries of the two sheep were small for their age and evidence of prior ovulation was not appreciated. In both sheep, the density of primordial follicles in the ovarian cortex was lower than normally found in ovine ovaries and primary follicle development was not observed. Mammary gland development was very limited. Results substantiate previous studies in other species that aneuploidy can be readily detected using SNP genotype allele intensity values generally already available, and the approach proposed in the present study was agnostic to genotype platform.
Conventionally perennial ryegrass evaluations are conducted under simulated grazing studies to identify varieties with the best phenotypic performance. However, cut-plot environments differ greatly to those experienced on commercial farms as varieties are not exposed to the same stress levels in test environments. It could be argued that plot-based testing regimes provide little direction to plant breeders in the development of advanced varieties. Varietal phenotypic performance needs to be quantified in ‘commercial’ situations. The objective of the current study was to evaluate the phenotypic performance of a range of perennial ryegrass varieties under commercial farm conditions. Monocultures of 11 Irish Recommended List perennial ryegrass varieties were sown on 66 commercial farms throughout Ireland where performance was evaluated over a 3-year period from 2013 to 2015, inclusive. A linear mixed model was used to quantify variety effects on grassland phenotypic performance characteristics. No significant variety effect was estimated for total, seasonal or silage herbage production. Despite the lack of variety effects, pairwise comparisons found significant performance differences between individual varieties. Grazed herbage yield is of primary importance and was shown to be correlated strongly with total production (0.71); Grazed herbage yield differed significantly by variety, with a range of 1927 kg dry matter (DM)/ha between the highest and lowest performing varieties. Sward quality (dry matter digestibility [DMD]) and density were influenced by variety with a range of 44 g/kg DM for DMD and 0.7 ground score units between the highest and lowest performing varieties. Results of the current study show that on-farm evaluation is effective in identifying the most suitable varieties for intensive grazing regimes, and the phenotypic variance identified among varieties performance for many traits should allow for improved genetic gain in areas such as DM production, persistence and grazing efficiency.
Cannabis use shows a robust dose-dependent relationship with psychosis risk among the general population. Despite this, it has been difficult to link cannabis use with risk for transitioning to a psychotic disorder among individuals at ultra-high risk (UHR) for psychosis. The present study examined UHR transition risk as a function of cannabis use characteristics which vary substantially between individuals including age of first use, cannabis abuse severity and a history of cannabis-induced attenuated psychotic symptoms (APS).
Method
Participants were 190 UHR individuals (76 males) recruited at entry to treatment between 2000 and 2006. They completed a comprehensive baseline assessment including a survey of cannabis use characteristics during the period of heaviest use. Outcome was transition to a psychotic disorder, with mean time to follow-up of 5.0 years (range 2.4–8.7 years).
Results
A history of cannabis abuse was reported in 58% of the sample. Of these, 26% reported a history of cannabis-induced APS. These individuals were 4.90 (95% confidence interval 1.93–12.44) times more likely to transition to a psychotic disorder (p = 0.001). Greater severity of cannabis abuse also predicted transition to psychosis (p = 0.036). However, this effect was mediated by higher abuse severity among individuals with a history of cannabis-induced APS.
Conclusions
Findings suggest that cannabis use poses risk in a subpopulation of UHR individuals who manifest cannabis-induced APS. Whether this reflects underlying genetic vulnerability requires further study. Nevertheless, findings reveal an important early marker of risk with potentially significant prognostic utility for UHR individuals.
The subsurface exploration of other planetary bodies can be used to unravel their geological history and assess their habitability. On Mars in particular, present-day habitable conditions may be restricted to the subsurface. Using a deep subsurface mine, we carried out a program of extraterrestrial analog research – MINe Analog Research (MINAR). MINAR aims to carry out the scientific study of the deep subsurface and test instrumentation designed for planetary surface exploration by investigating deep subsurface geology, whilst establishing the potential this technology has to be transferred into the mining industry. An integrated multi-instrument suite was used to investigate samples of representative evaporite minerals from a subsurface Permian evaporite sequence, in particular to assess mineral and elemental variations which provide small-scale regions of enhanced habitability. The instruments used were the Panoramic Camera emulator, Close-Up Imager, Raman spectrometer, Small Planetary Linear Impulse Tool, Ultrasonic drill and handheld X-ray diffraction (XRD). We present science results from the analog research and show that these instruments can be used to investigate in situ the geological context and mineralogical variations of a deep subsurface environment, and thus habitability, from millimetre to metre scales. We also show that these instruments are complementary. For example, the identification of primary evaporite minerals such as NaCl and KCl, which are difficult to detect by portable Raman spectrometers, can be accomplished with XRD. By contrast, Raman is highly effective at locating and detecting mineral inclusions in primary evaporite minerals. MINAR demonstrates the effective use of a deep subsurface environment for planetary instrument development, understanding the habitability of extreme deep subsurface environments on Earth and other planetary bodies, and advancing the use of space technology in economic mining.
Peer volunteers can be key to delivering effective social cognitive interventions due to increased potential for social modeling. We consulted peer volunteers who had just taken part in an 8-week social and nutritional mealtime intervention with older adults living alone, to seek their evaluation of the intervention.
Methods:
Semi-structured focus groups were used with a total of 21 volunteers (17 female) and two facilitators. Thematic analysis was used to interrogate the data.
Results:
Six themes (16 sub-themes) are discussed. Peer volunteers described the importance of the socializing aspect of the intervention, of pairing considerations and compatibility in peer interventions, of considering the needs of the participant, of benefits to the volunteers, and of the practical considerations of conducting an intervention. Volunteers also discussed considerations for future research and services for older adults living alone.
Conclusions:
Volunteers found their involvement in the intervention to be personally beneficial, and revealed some valuable considerations for the researchers to take forward to future research. Results are pertinent to intervention design and could inform future social cognitive and other peer-oriented interventions for older adults living alone.
Physical health and, in particular, frailty may be associated with psychological factors among older adults. We aimed to investigate the relationships between aspects of psychological distress and progression of frailty over time among older adults.
Methods
We used a longitudinal observational study design with 624 participants aged over 60 years (mean age=72.75, s.d.=7.21, 68% female) completing a baseline comprehensive biopsychosocial geriatric assessment, and 447 returning for a follow-up assessment 2 years later. Aspects of psychological distress, physical health, and frailty were analysed for the purposes of this study. We employed a series of logistic regression analyses to determine psychological predictors of changing states of aspects of frailty over time.
Results
With individual components of frailty, neuroticism and age predicted negative transitions of exhaustion and grip strength, respectively, whereas age alone was a predictor of transitions in overall frailty scores based on four components.
Conclusion
We conclude that neuroticism and age may impact upon physical frailty and its progression over time in an ageing population. These findings may reflect the tendency for those with high levels of neuroticism to endorse negative symptoms, or alternatively, neuroticism may result in exhaustion via worry in an older population. Further research is required to further elucidate this relationship.
It is widely accepted that people with mental illness have increased risk of cardiometabolic complications such as obesity and type 2 diabetes mellitus. What is less well known is that individuals with diabetes have an increased risk of brain health complications including depression, cognitive impairment and dementia. These conditions can adversely influence disease self-management and further increase risk of other diabetes complications.
Aim
The aim of this paper is to highlight the increased risk of brain health complications in populations with diabetes in order to promote awareness of such complications among healthcare professionals and encourage timely intervention.
Methods
An overview of the prevalence and potential mechanisms linking depression and cognitive impairment with diabetes as well as implications for detection, management and brain health protection, based on a narrative review of the literature.
Conclusions
Early detection and effective management of depression and cognitive impairment among individuals with diabetes has the potential to minimise adverse health outcomes. In order to promote screening healthcare professionals caring for individuals with diabetes in all settings must be aware of the increased risk of brain health complications in this vulnerable population.
The UK Government has recently implemented large-scale public-sector funding cuts and substantial welfare reform. Groups within civil society are being encouraged to fill gaps in service provision, and ‘social innovation’ has been championed as a means of addressing social exclusion, such as that caused by worklessness, a major impediment to citizens being able to access money, power and resources, which are key social determinants of health. The aim of this article is to make the case for innovative ‘upstream’ approaches to addressing health inequalities, and we discuss three prominent social innovations gaining traction: microcredit for enterprise; social enterprise in the form of Work Integration Social Enterprises (WISEs); and Self Reliant Groups (SRGs). We find that while certain social innovations may have the potential to address health inequalities, large-scale research programmes that will yield the quality and range of empirical evidence to demonstrate impact, and, in particular, an understanding of the causal pathways and mechanisms of action, simply do not yet exist.