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BACKGROUND: Outpatient care for patients with heart valve disease (HVD) is best provided by valve clinics delivered by specialists. Modern day practice in the United Kingdom (UK) is currently poorly understood and has not been evaluated for nearly a decade. Furthermore, the COVID 19 pandemic changed the management of many chronic diseases, and how this has impacted patients with heart valve disease is unclear. METHODS: A British Heart Valve Society survey was sent to 161 hospitals throughout the UK. RESULTS: There was a general valve clinic in 46 of the 68 hospitals (68%), in 19 of 23 Heart Centres (83%) and 29 of 45 DGHs (64%). Across all settings, 3824 new patients and 17,980 follow up patients were seen in valve clinics per annum. The mean number of patients per hospital were 197 (median 150, range 48-550) for new patients and 532 (median 400, range 150-2000) for follow up. On the day echocardiography was available in 55% of valve clinics. In patients with severe HVD, serum brain natriuretic peptide (BNP) was measured routinely in 39% of clinics and exercise testing routinely performed in 49% of clinics. A patient helpline was available in 27% of clinics. 78% of centres with a valve clinic had a valve multidisciplinary team meeting (MDT). 45% centres had an MDT co-ordinator and MDT outcomes were recorded on a database in 64%. COVID-19 had a major impact on valve services in 54 (95%) hospitals. CONCLUSIONS: There has been an increase in the number of valve clinics since 2015 from 21 to 68% but the penetration is still well short of the expected 100%, meaning that valve clinics only serve a small proportion of patients requiring surveillance for HVD. COVID-19 had a major impact on the care of patients with HVD in the majority of UK centres surveyed.

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Introduction: Critical-sized long bone defects represent a major therapeutic challenge and current treatment strategies are not without complication. Tissue engineering holds much promise for these debilitating injuries; however, these strategies often fail to successfully translate from rodent studies to the clinical setting. The dog represents a strong model for translational orthopedic studies, however such studies should be optimized in pursuit of the Principle of the 3R's of animal research (replace, reduce, refine). The objective of this study was to refine a canine critical-sized femoral defect model using an angle-stable interlocking nail (AS-ILN) and reduce total animal numbers by performing imaging, biomechanics, and histology on the same cohort of dogs. Methods: Six skeletally mature hounds underwent a 4 cm mid-diaphyseal femoral ostectomy followed by stabilization with an AS-ILN. Dogs were assigned to autograft (n = 3) or negative control (n = 3) treatment groups. At 6, 12, and 18 weeks, healing was quantified by ordinal radiographic scoring and quantified CT. After euthanasia, femurs from the autograft group were mechanically evaluated using an established torsional loading protocol. Femurs were subsequently assessed histologically. Results: Surgery was performed without complication and the AS-ILN provided appropriate fixation for the duration of the study. Dogs assigned to the autograft group achieved radiographic union by 12 weeks, whereas the negative control group experienced non-union. At 18 weeks, median bone and soft tissue callus volume were 9,001 mm3 (range: 4,939-10,061) for the autograft group and 3,469 mm3 (range: 3,085-3,854) for the negative control group. Median torsional stiffness for the operated, autograft treatment group was 0.19 Nm/° (range: 0.19-1.67) and torque at failure was 12.0 Nm (range: 1.7-14.0). Histologically, callus formation and associated endochondral ossification were identified in the autograft treatment group, whereas fibrovascular tissue occupied the critical-sized defect in negative controls. Conclusion: In a canine critical-sized defect model, the AS-ILN and described outcome measures allowed refinement and reduction consistent with the Principle of the 3R's of ethical animal research. This model is well-suited for future canine translational bone tissue engineering studies.

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Genomic tools have improved the ability to manage bison populations and enhanced efforts to conserve this iconic species. These tools have been particularly useful for detecting introgression of cattle genome within bison herds but are limited by the need to use the cattle genome as a surrogate for mapping reads. This complicates efforts to distinguish the species of origin of chromosomal segments in individual bison at the genomic level. An assembly (Bison_UMD1.0) based on 75X genome coverage by Illumina and 454 reads was generated using the MaSuRCA assembler, generating a 2.81 Gigbases de novo reference genome from American bison. Comparison of bison and domestic cattle references identified 28 443 364 single nucleotide variants and 2 627 645 insertions/deletions distinguishing the species. Sequence alignment of an additional 12 modern bison samples and two historic bison samples to domestic cattle and bison references provides a dataset of genomic variants defining the different species and within-species variation. This first annotated draft assembly represents a resource for the management and conservation of bison, as well as a means to study the effects on the genome of interspecies hybridization. The comparisons of historical bison sequences with the new bison reference identified genomic differences between modern and pre-population bottleneck bison. The results support the application of genomics to enhance future research on disease, the establishment of satellite conservation herds and insight into bison and cattle speciation. The first genome assembly for bison and dataset provides a foundation that can be built upon as genetic technologies improve over the years.

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OBJECTIVE: The primary objective of this study was to test the hypotheses that compared to IVF cycles undergoing preimplantation genetic testing for aneuploidy (PGT-A) with or without testing for monogenic disorders (PGT-M), IVF cycles undergoing PGT for structural rearrangements (PGT-SR) will have (1) a poorer blastocyst conversion rate and (2) fewer usable blastocysts available for transfer. Secondarily, the study aimed to compare pregnancy outcomes among PGT groups. PATIENTS: Retrospective cohort study including cycles started from January 1, 2012, to March 30, 2020, with the intent of pursuing PGT-A, PGT-A with PGT-M, and PGT-SR, with trophectoderm biopsy on days 5 or 6. RESULTS: A total of 658 women underwent 902 cycles, including 607 PGT-A, 216 PGT-A&M, and 79 PGT-SR cycles. When compared with the blastocyst conversion rate for the PGT-A group (59.4%), and after adjustment for patient age, total number of mature oocytes, BMI, and ICSI, there were no significant differences for either the PGT-A&M (69.7%, aRR 1.03, 95% CI 0.96-1.10) or PGT-SR (63.2%, aRR1.04, 95% CI 0.96-1.13) groups. Compared to the PGT-A group, the proportion of usable blastocysts was statistically significantly lower in the PGT-SR group: 35.1% versus 24.4% (aRR 0.57, 95% CI 0.46-0.71) and the PGT-A&M group: 35.1% versus 31.5% (aRR 0.68, 95% CI 0.58-0.81). Implantation, pregnancy, and miscarriage rates were equivalent for all groups. CONCLUSION: Patients with structural rearrangements have similar blastocyst development but significantly fewer usable blastocysts available for transfer compared to PGT-A testers. Nevertheless, with the transfer of a usable embryo, PGT-SR testers perform as well as those testing for PGT-A.

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AIMS: Myocardial perfusion imaging during hyperaemic stress is commonly used to detect coronary artery disease. The aim of this study was to investigate the relationship between left ventricular global longitudinal strain (GLS), strain rate (GLSR), myocardial early (E') and late diastolic velocities (A') with adenosine stress first-pass perfusion cardiovascular magnetic resonance (CMR) imaging. METHODS AND RESULTS: 44 patients met the inclusion criteria and underwent CMR imaging. The CMR imaging protocol included: rest/stress horizontal long-axis (HLA) cine, rest/stress first-pass adenosine perfusion and late gadolinium enhancement imaging. Rest and stress HLA cine CMR images were analysed using feature-tracking software for the assessment of myocardial deformation. The presence of perfusion defects was scored on a binomial scale. In patients with hyperaemia-induced perfusion defects, rest global longitudinal strain GLS (-16.9 ± 3.7 vs. -19.6 ± 3.4; p-value = 0.02), E' (-86 ± 22 vs. -109 ± 38; p-value = 0.02), GLSR (69 ± 31 vs. 93 ± 38; p-value = 0.01) and stress GLS (-16.5 ± 4 vs. -21 ± 3.1; p < 0.001) were significantly reduced when compared with patients with no perfusion defects. Stress GLS was the strongest independent predictor of perfusion defects (odds ratio 1.43 95% confidence interval 1.14-1.78, p-value <0.001). A threshold of -19.8% for stress GLS demonstrated 78% sensitivity and 73% specificity for the presence of hyperaemia-induced perfusion defects. CONCLUSIONS: At peak myocardial hyperaemic stress, GLS is reduced in the presence of a perfusion defect in patients with suspected coronary artery disease. This reduction is most likely caused by reduced endocardial blood flow at maximal hyperaemia because of transmural redistribution of blood flow in the presence of significant coronary stenosis.

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Two siblings with a severe multiorgan polycystic disease presenting in the neonatal period were identified. Their genetic testing identified compound heterozygous NPHP3 gene mutations, parents being heterozygous carriers. The mutations included a splice-site (c.958-2A>G) and a missense mutation (c.2342G>A; p.G781D), both being extremely rare. NPHP3 encodes for nephrocystin 3 present on the cilia-centrosome complex. We hypothesize that these mutations lead to defective cilia-based signaling, required for normal development of the renal, pancreatic, biliary and portal system. This report outlines a rare neonatal ciliopathy presentation of NPHP3 mutations leading to severe multiorgan failure in two siblings.

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Over the past few decades, the mainstay of hypertension management has been pharmacological therapy; however, there is now a growing body of evidence that drug-resistant hypertension can be managed effectively by renal artery ablation. Several studies have documented the feasibility and safety of this treatment, although data regarding long-term outcomes are still emerging. Atrial fibrillation (AF) and hypertension commonly coexist, and recent work has demonstrated improved outcomes from catheter ablation of AF with concomitant renal artery denervation at little extra cost in terms of time and resource. The aim of this review is to explore the link between hypertension and AF, the synergistic effect of renal artery ablation on AF ablation, explain how this may work and address unanswered questions.

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OBJECTIVE: To determine if the instant approval (IA) process differs from the traditional prior authorization (PA) process in preferred drug channeling, resultant gaps in therapy, and provider dissatisfaction. STUDY DESIGN: An interrupted time series analysis using pharmacy claims and a retrospective cohort study. METHODS: The study assessed changes in preferred drug use and subsequent cost reductions. A retrospective cohort study determined if the IA process produced fewer gaps in therapy than the PA process. Provider acceptance of the IA process was assessed using a brief survey of 240 randomly selected primary care practices. RESULTS: Market share for preferred proton pump inhibitors quadrupled from a range of 17.6% to 19.3% at baseline to 76% in the first month after implementation of the new IA policy. Most practices (81.1%) reported reduced administrative burden with the IA process. The median gaps between medication fills for patients using IA were approximately one-half those of patients using PA (P <.001) and were one-fourth in a subset of highly adherent, regularly filling patients (P <.001). CONCLUSIONS: Instant approval may be more patient friendly and prescriber friendly than PA as assessed by a proxy measure for access (gap in therapy) and physician-reported acceptance. Despite its ease of use, IA does not seem to reduce switching to preferred drugs.

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The United States leads the world in health care costs but ranks far below many developed countries in health outcomes. Finding ways to narrow this gap remains elusive. This article describes the response of one state to establish community health networks to achieve quality, utilization, and cost objectives for the care of its Medicaid recipients. The program, known as Community Care of North Carolina, is an innovative effort organized and operated by practicing community physicians. In partnership with hospitals, health departments, and departments of social services, these community networks have improved quality and reduced cost since their inception a decade ago. The program is now saving the State of North Carolina at least $160 million annually. A description of this experience and the lessons learned from it can inform others seeking to implement effective systems of care for patients with chronic illness.

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BACKGROUND: Warfarin therapy substantially reduces stroke in atrial fibrillation (AF), yet medical literature reports it is only prescribed in 15-60% of eligible patients. No current national benchmarks for warfarin use in AF patients exist, and it is unclear whether the reported poor compliance represents current rates within primary care practices. The primary study objective was to measure the rate of warfarin use in eligible, high-risk AF patients in a large southeastern group family practice. Secondary objectives were to report the demographics, stroke-risk profiles, contraindications, and reasons for discontinuation of warfarin therapy METHODS: A retrospective chart review was performed on all active patients with documented AF in a large southeastern group family practice/residency between July 1, 2000 and June 30, 2002. Data was abstracted on warfarin use, contraindications, stroke risk, and reasons for discontinuation. RESULTS: Four hundred ninety-one (491) patients were identified from the electronic billing system as potential study subjects. Two hundred eighty-three (283) patients met study criteria, with 210 patients considered to be at high-risk of stroke without contraindications to warfarin therapy. Ninety-four percent (198/210) of these patients were prescribed warfarin during the study period, and 87% (172/198) continued warfarin throughout the study period. CONCLUSION: Family physicians in this practice prescribe warfarin in AF more frequently than published rates demonstrating that high rates of physician adherence to standards are achievable in primary care. Most patients in this setting were considered high-risk for stroke.

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