Community health navigator-assisted transition of care from hospital to community: protocol for a randomised controlled trial.

INTRODUCTION: The objective of this parallel group, randomised controlled trial is to evaluate a community health navigator (CHN) intervention provided to patients aged over 40 years and living with chronic health conditions to transition from hospital inpatient care to their homes. Unplanned hospital readmissions are costly for the health system and negatively impact patients. METHODS AND ANALYSIS: Patients are randomised post hospital discharge to the CHN intervention or usual care. A comparison of outcomes between intervention and control groups will use multivariate regression techniques that adjust for age, sex and any independent variables that are significantly different between the two groups, using multiple imputation for missing values. Time-to-event analysis will examine the relationship between seeing a CHN following discharge from the index hospitalisation and reduced rehospitalisations in the subsequent 60 days and 6 months. Secondary outcomes include medication adherence, health literacy, quality of life, experience of healthcare and health service use (including the cost of care). We will also conduct a qualitative assessment of the implementation of the navigator role from the viewpoint of stakeholders including patients, health professionals and the navigators themselves. ETHICS APPROVAL: Ethics approval was obtained from the Research Ethics and Governance Office, Sydney Local Health District, on 21 January 2022 (Protocol no. X21-0438 and 2021/ETH12171). The findings of the trial will be disseminated through peer-reviewed journals and national and international conference presentations. Data will be deposited in an institutional data repository at the end of the trial. This is subject to Ethics Committee approval, and the metadata will be made available on request. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN 12622000659707). ARTICLE SUMMARY: The objective of this trial is to evaluate a CHN intervention provided to patients aged over 40 years and living with chronic health conditions to transition from hospital inpatient care to their homes.

The effect of surgical complications on long-term prognosis following oesophagectomy.

INTRODUCTION: Complications are frequent after oesophagectomy, and there is evidence these adversely impact long-term prognosis. However, the effect of multiple complications, and the absolute magnitude of effect on survival is unclear. This study aimed to examine these effects in a single high-volume UK unit. METHODS: Patients undergoing oesophagectomy for cancer and who survived to 90 days post-oesophagectomy were analysed. Complications were graded according to the Clavien-Dindo (CD) classification and the Comprehensive Complication Index (CCI). The effect and magnitude of effect of complications on survival were assessed using multivariable cox regression and the risk-adjusted population attributable fraction. RESULTS: In total, 380 patients were included. Complications occurred in 251 (66.1%). Suffering ≥3 complications (HR 1.89, 95%CI 1.13-3.16, p = 0.015) or an unplanned escalation in care (HR 2.22, 95%CI 1.43-3.45, p < 0.001) significantly reduced survival whereas pulmonary complications and anastomotic leak did not. Patients with a CCI>30 had worse overall survival (HR 1.91, 95%CI 1.32-2.76, p < 0.001) and CCI>30 due to multiple minor complications gave a worse prognosis compared to CCI>30 due to major complications (HR 2.44, 95%CI 1.14-5.20, p = 0.022). An estimated 9.1% (95%CI 3.4-14.4%) of deaths at 5 years were attributable to a CCI>30. CONCLUSION: Long-term survival following oesophagectomy for cancer is significantly affected by complications and the cumulative effect of multiple complications. Interestingly, multiple minor complications had a worse effect on survival than major complications. The absolute magnitude of effect is substantial: minimising all types of postoperative complications could have significant benefit to overall outcomes.

Moral distress in rural veterinarians as an outcome of the Mycoplasma bovis incursion in southern New Zealand.

AIMS: To gain insight into the world of rural veterinarians during the Mycoplasma bovis incursion within southern Aotearoa New Zealand by exploring their experiences during the incursion, and to understand the consequences, positive and negative, of these experiences. METHODS: A qualitative social science research methodology, guided by the philosophical paradigm of pragmatism, was used to collect data from an information-rich sample (n = 6) of rural veterinarians from Otago and Southland. Interview and focus group techniques were used, both guided by a semi-structured interview guide. Veterinarians were asked a range of questions, including their role within the incursion; whether their involvement had any positive or negative impact for them; and their experience of conflicting demands. Analysis of the narrative data collected was guided by Braun and Clarke's approach to reflexive thematic analysis. RESULTS AND FINDINGS: All six participants approached agreed to participate. Analysis of the data provided an understanding of the trauma they experienced during the incursion. An overarching theme of psychological distress was underpinned by four sub-themes, with epistemic injustice and bearing witness the two sub-themes reported to be associated with the greatest experience of psychological distress. These, along with the other two identified stressors, led to the experience of moral distress, with moral residue and moral injury also experienced by some participants. CONCLUSIONS: Eradication programmes for exotic diseases in production animals inevitably have an impact on rural veterinarians, in their role working closely with farmers. Potentially, these impacts could be positive, recognising and utilising veterinarians' experience, skills and knowledge base. This study, however, illustrates the significant negative impacts for some rural veterinarians exposed to the recent M. bovis eradication programme in New Zealand, including experiences of moral distress and moral injury. Consequently, this eradication programme resulted in increased stress for study participants. There is a need to consider how the system addresses future exotic disease incursions to better incorporate and utilise the knowledge and skills of the expert workforce of rural veterinarians and to minimise the negative impacts on them. CLINICAL RELEVANCE: To date, the experience of moral distress by rural veterinarians during exotic disease incursions has been under-reported globally and unexplored in New Zealand. The findings from this study contribute further insights to the existing limited literature and provide guidance on how to reduce the adverse experiences on rural veterinarians during future incursions. ABBREVIATIONS: MPI: Ministry for Primary Industries; PITS: Perpetration-induced traumatic stress; PTSD: Post-traumatic stress disorder.

Assessment of Free-Living Cadence Using ActiGraph Accelerometers Between Individuals With and Without Anterior Cruciate Ligament Reconstruction.

CONTEXT: Anterior cruciate ligament reconstruction (ACLR) and gait speed are risk factors for developing knee osteoarthritis (OA). Measuring minute-level cadence during free-living activities may aid in identifying individuals at elevated risk of developing slow habitual gait speed and, in the long term, OA. OBJECTIVE: To assess differences in peak 1-minute cadence and weekly time in different cadence intensities between individuals with and without ACLR. DESIGN: Cross-sectional study. SETTING: Short-term, free-living conditions. PATIENTS OR OTHER PARTICIPANTS: A total of 57 participants with ACLR (34 women, 23 men; age = 20.9 ± 3.2 years, time since surgery = 28.7 ± 17.7 months) and 42 healthy control participants (22 women, 20 men; age = 20.7 ± 1.7 years). MAIN OUTCOME MEASURE(S): Each participant wore a physical activity monitor for 7 days. Data were collected at 30 Hz, processed in 60-second epochs, and included in the analyses if the activity monitor was worn for at least 10 hours per day over 4 days. Mean daily steps, peak 1-minute cadence, and weekly minutes spent at 60 to 79 (slow walking), 80 to 99 (medium walking), 100 to 119 (brisk walking), ≥100 (moderate- to vigorous-intensity ambulation), and ≥130 (vigorous-intensity ambulation) steps per minute were calculated. One-way analyses of covariance were conducted to determine differences between groups, controlling for height and activity-monitor wear time. RESULTS: Those with ACLR took fewer daily steps (8422 ± 2663 versus 10 033 ± 3046 steps; P = .005) and spent fewer weekly minutes in moderate- to vigorous-intensity cadence (175.8 ± 116.5 minutes versus 218.5 ± 137.1 minutes; P = .048) than participants without ACLR. We observed no differences in minutes spent at slow (ACLR = 77.4 ± 40.5 minutes versus control = 83.9 ± 34.3 minutes; P = .88), medium (ACLR = 71.6 ± 40.2 minutes versus control = 82.9 ± 46.8 minutes; P = .56), brisk (ACLR = 115.3 ± 70.3 minutes versus control = 138.3 ± 73.3 minutes; P = .18), or vigorous-intensity (ACLR = 24.3 ± 36.5 minutes versus control = 38.1 ± 60.9 minutes; P = .10) cadences per week. CONCLUSIONS: Participants with ACLR walked approximately 40 fewer minutes per week in moderate- to vigorous-intensity cadence than participants without ACLR. Increasing the time spent at cadence ≥100 steps per minute and overall volume of physical activity may be useful as interventional targets to help reduce the risk of early development of OA after ACLR.

Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma.

BACKGROUND: This multicentre cohort study sought to define a robust pathological indicator of clinically meaningful response to neoadjuvant chemotherapy in oesophageal adenocarcinoma. METHODS: A questionnaire was distributed to 11 UK upper gastrointestinal cancer centres to determine the use of assessment of response to neoadjuvant chemotherapy. Records of consecutive patients undergoing oesophagogastric resection at seven centres between January 2000 and December 2013 were reviewed. Pathological response to neoadjuvant chemotherapy was assessed using the Mandard Tumour Regression Grade (TRG) and lymph node downstaging. RESULTS: TRG (8 of 11 centres) was the most widely used system to assess response to neoadjuvant chemotherapy, but there was discordance on how it was used in practice. Of 1392 patients, 1293 had TRG assessment; data were available for clinical and pathological nodal status (cN and pN) in 981 patients, and TRG, cN and pN in 885. There was a significant difference in survival between responders (TRG 1-2; median overall survival (OS) not reached) and non-responders (TRG 3-5; median OS 2·22 (95 per cent c.i. 1·94 to 2·51) years; P < 0·001); the hazard ratio was 2·46 (95 per cent c.i. 1·22 to 4·95; P = 0·012). Among local non-responders, the presence of lymph node downstaging was associated with significantly improved OS compared with that of patients without lymph node downstaging (median OS not reached versus 1·92 (1·68 to 2·16) years; P < 0·001). CONCLUSION: A clinically meaningful local response to neoadjuvant chemotherapy was restricted to the small minority of patients (14·8 per cent) with TRG 1-2. Among local non-responders, a subset of patients (21·3 per cent) derived benefit from neoadjuvant chemotherapy by lymph node downstaging and their survival mirrored that of local responders.

BDNF During Withdrawal.

Among the adaptations observed following drugs of abuse consumption, BDNF levels are widely altered in both brain and periphery. In this chapter, we first reviewed these adaptations in preclinical studies, in both juveniles and adult animals. A particular focus was made on protracted withdrawal as incubation is often associated with an increase in central BDNF levels. Then, we reported mixed results regarding the role of BDNF in drug-seeking behavior in animals as BDNF can either enhance reinstatement or have protective properties. Finally, we reviewed recent clinical studies that provide insight into the potential of BDNF to be a good biomarker of vulnerability to relapse.

The Development, Application and Analysis of an Enhanced Recovery Programme for Major Oesophagogastric Resection.

BACKGROUND: Enhanced recovery programmes improve outcomes in surgery, but their implementation after upper gastrointestinal resection has been limited. The aim of this study was to compare short-term outcomes for patients undergoing oesophagogastric surgery in an enhanced recovery programme (EROS). METHODS: EROS was developed after a multidisciplinary meeting by multiple rounds of revision. EROS was applied to all patients undergoing major upper GI resection at a university teaching hospital in the UK from 20/9/13, with data reviewed at 18/09/15. EROS was assessed to identify predictors for compliance. RESULTS: One hundred six patients underwent major upper GI resection including 81 oesophagectomies, 24 gastrectomies and 1 colonic interposition graft. Major complications (Clavien Dindo ≥3) occurred in 12 patients with 1 in-hospital death. Thirty-five patients (44%) were discharged on target day 8 of the EROS programme. Age and complications were independently associated with missing this discharge target. CONCLUSION: Enhanced recovery is feasible and safe after major upper gastrointestinal surgery.

Systematic review and meta-analysis of immunohistochemical prognostic biomarkers in resected oesophageal adenocarcinoma.

BACKGROUND: Oesophageal adenocarcinoma (OAC) is one of the fastest rising malignancies with continued poor prognosis. Many studies have proposed novel biomarkers but, to date, no immunohistochemical markers of survival after oesophageal resection have entered clinical practice. Here, we systematically review and meta-analyse the published literature, to identify potential biomarkers. METHODS: Relevant articles were identified via Ovid medline 1946-2013. For inclusion, studies had to conform to REporting recommendations for tumor MARKer (REMARK) prognostic study criteria. The primary end-point was a pooled hazard ratio (HR) and variance, summarising the effect of marker expression on prognosis. RESULTS: A total of 3059 articles were identified. After exclusion of irrelevant titles and abstracts, 214 articles were reviewed in full. Nine molecules had been examined in more than one study (CD3, CD8, COX-2, EGFR, HER2, Ki67, LgR5, p53 and VEGF) and were meta-analysed. Markers with largest survival effects were COX-2 (HR=2.47, confidence interval (CI)=1.15-3.79), CD3 (HR=0.51, 95% CI=0.32-0.70), CD8 (HR=0.55, CI=0.31-0.80) and EGFR (HR=1.65, 95% CI=1.14-2.16). DISCUSSION: Current methods have not delivered clinically useful molecular prognostic biomarkers in OAC. We have highlighted the paucity of good-quality robust studies in this field. A genome-to-protein approach would be better suited for the development and subsequent validation of biomarkers. Large collaborative projects with standardised methodology will be required to generate clinically useful biomarkers.

Thoracoabdominal herniation--but not as you know it.

Thoracoabdominal hernias are uncommon following blunt trauma. If diaphragmatic rupture does occur, the abdominal viscera can herniate into the thorax through the diaphragm. We report a rare case of thoracoabdominal herniation in which the bowel herniated through the lateral abdominal wall, migrating cranially and entering the thorax through an intercostal defect. This case highlights the need for early and definitive surgical repair.

A prospective comparison of totally minimally invasive versus open Ivor Lewis esophagectomy.

The majority of esophagectomies in Western parts of the world are performed by a transthoracic approach reflecting the prevalence of adenocarcinoma of the lower esophagus or esophagogastric junction. Minimally invasive esophagectomy (MIE) has been reported in a variety of formats, but there are no series that directly compare totally minimally invasive thoracolaparoscopic 2 stage esophagectomy (MIE-2) with open Ivor Lewis (IVL). A prospective single-center cohort study of patients undergoing elective MIE-2 or IVL between January 2005 and November 2010 was performed. Short-term clinicopathologic outcomes were recorded using validated systems. One hundred and six patients (median age 66, range 36-85, 88 M : 18 F) underwent two-stage esophagectomy (53 MIE-2 and 53 IVL). Patient demographics (age, sex, body mass index, American Society of Anesthesiologists grade, tumor characteristics, neoadjuvant chemotherapy, and TNM stage) were comparable between the two groups. Outcomes for MIE-2 and IVL were comparable for anastomotic leak rates (5 [9%] vs. 2 [4%], P= 0.241), resection margin clearance (R0) (43 [81%] vs. 38 [72%], P= 0.253), median lymph node yield (19 vs. 18, P= 0.584), and median length of stay (12 [range 7-91] vs. 12 [range 7-101] days), respectively. Blood loss was significantly less for MIE-2 compared with IVL (median 300 [range 0-1250] mL vs. 400 [range 0-3000] mL, respectively, P= 0.021). MIE-2 in this series of selected patients supports its efficacy, when performed by an experienced minimally invasive surgical team. A well-designed multicenter trial addressing clinical effectiveness is now required.

Short- and long-lasting behavioral and neurochemical adaptations: relationship with patterns of cocaine administration and expectation of drug effects in rats.

Cocaine dependence is a significant public health problem, characterized by periods of abstinence. Chronic exposure to drugs of abuse induces important modifications on neuronal systems, including the dopaminergic system. The pattern of administration is an important factor that should be taken into consideration to study the neuroadaptations. We compared the effects of intermittent (once daily) and binge (three times a day) cocaine treatments for 1 (WD1) and 14 (WD14) days after the last cocaine injection on spontaneous locomotor activity and dopamine (DA) levels in the nucleus accumbens (Nac). The intermittent treatment led to a spontaneous increase in DA (WD1/WD14), and in locomotor activity (WD1) at the exact hour which rats were habituated to receive a cocaine injection. These results underline that taking into consideration the hours of the day at which the experiments are performed is crucial. We also investigated these behavioral and neurochemical adaptations in response to an acute cocaine challenge on WD1 and WD14. We observed that only the binge treatment led to sensitization of locomotor effects of cocaine, associated to a DA release sensitization in the Nac, whereas the intermittent treatment did not. We demonstrate that two different patterns of administration induced distinct behavioral and neurochemical consequences. We unambiguously demonstrated that the intermittent treatment induced drug expectation associated with higher basal DA level in the Nac when measured at the time of chronic cocaine injection and that the binge treatment led to behavioral and sensitization effects of cocaine.

Extrinsic Notch ligand Delta-like 1 regulates tip cell selection and vascular branching morphogenesis.

RATIONALE: In developing blood vessels, single endothelial cells (ECs) specialize into tip cells that sense vascular endothelial growth factor (VEGF) and contribute to vessel sprouting and branch formation. Tip cell differentiation is inhibited through lateral Notch signaling between ECs, which is controlled by Notch ligands expressed in vessel sprouts. The contribution of the Notch ligand Delta-like (Dll) 1 herein is unknown. OBJECTIVE: To investigate the role of Dll1 in vascular morphogenesis and tip cell formation in the mouse retina. METHODS AND RESULTS: Mice with heterozygous deletion of Dll1 had fewer tip cells during angiogenic sprouting of the superficial vascular plexus but also showed impaired vessel branching into deeper retinal layers and impaired deep plexus angiogenesis. Interestingly, the formation of vertical branches was also guided by filopodia-extending ECs located at the tip of branches, consistent with tip cells, which emerged from established vessels to form a secondary plexus within the deeper neuronal cell layers. During both phases of vascular patterning, Dll1 was not expressed in ECs but in the superficial neuronal layer in close contact with expanding vessels, where Dll1 expression coincided with tip cell formation in a spatiotemporal manner. In vitro, culture of ECs on DLL1 induced essential tip cell genes, including Dll4, VEGF receptor 3, and ephrin-B2, and stimulated VEGF responsiveness and vascular network formation. CONCLUSIONS: Dll1 acts as an extrinsic cue involved in tip cell selection, which directs vessel sprouting and branch formation.

[Cannabis withdrawal syndrome in patients with cannabis dependence only, and in patients with cannabis and opioid dependence]. / Syndrome de sevrage au cannabis dans une population de patients mono- et polydépendants (cannabis et opiacés).

BACKGROUND: The cannabis withdrawal syndrome occurs after cannabis cessation in more than 50% of dependent smokers. But although opioid-dependent patients are more frequently cannabis users and cannabis-dependent than the general population, the frequency and phenomenology of cannabis withdrawal symptoms in this specific population is unknown. Our hypothesis was that cannabis-dependent patients with current opioid dependence would experience the same withdrawal syndrome after cannabis cessation. OBJECTIVE: To describe cannabis withdrawal symptoms in cannabis-only dependent patients and in cannabis-dependent patients with current opioid dependence. METHODS: Using retrospective interviews, we evaluated the number and duration of six cannabis withdrawal symptoms in two groups: 56 cannabis-dependent patients without and 43 cannabis dependent patients with current opioid dependence. Cannabis and opioid dependence diagnoses were defined with DSM IV criteria using the MINI structured interview. RESULTS: The two groups were not different in terms of age of onset of cannabis use, and number of cannabis joints smoked at the time of the cannabis cessation attempt. The frequency of a cannabis withdrawal syndrome (defined as at least two different symptoms) did not differ in the two groups (65%). Neither was the proportion of subjects with the following symptoms: appetite or weight loss (30.8%), irritability (45.1%), anxiety (56%), aggression (36.3%) and restlessness (45.1%). Patients with cannabis dependence and current opioid dependence were more likely to report sleep disturbances (79.1 vs. 53.6%, chi(2)=6.91, P=0.007). The median duration of this cannabis withdrawal syndrome was 20 days post-cessation. CONCLUSION: This is, to our knowledge, the first study describing cannabis withdrawal syndrome in cannabis-dependent patients with current opioid dependence. These patients experience a cannabis withdrawal syndrome as often as cannabis-only dependent subjects, but describe more frequently sleep disturbances. This high rate of sleep disturbances may cause relapse to cannabis use.

Improvement of fractional flow reserve and collateral flow by treatment with external counterpulsation (Art.Net.-2 Trial).

BACKGROUND: Arteriogenesis (collateral artery growth) is nature's most efficient rescue mechanism to overcome the fatal consequences of arterial occlusion or stenosis. The goal of this trial was to investigate the effect of external counterpulsation (ECP) on coronary collateral artery growth. MATERIALS AND METHODS: A total of 23 patients (age 61 +/- 2.5 years) with stable coronary artery disease and at least one haemodynamic significant stenosis eligible for percutaneous coronary intervention were prospectively recruited into the two study groups in a 2 : 1 manner (ECP : control). One group (ECP group, n = 16) underwent 35 1-h sessions of ECP in 7 weeks. In the control group (n = 7), the natural course of collateral circulation over 7 weeks was evaluated. All patients underwent a cardiac catheterization at baseline and after 7 weeks, with invasive measurements of the pressure-derived collateral flow index (CFIp, primary endpoint) and fractional flow reserve (FFR). RESULTS: In the ECP group, the CFIp (from 0.08 +/- 0.01 to 0.15 +/- 0.02; P < 0.001) and FFR (from 0.68 +/- 0.03 to 0.79 +/- 0.03; P = 0.001) improved significantly, while in the control group no change was observed. Only the ECP group showed a reduction of the Canadian Cardiovascular Society (CCS, P = 0.008) and New York Heart Association (NYHA, P < 0.001) classification. CONCLUSION: In this study, we provide direct functional evidence for the stimulation of coronary arteriogenesis via ECP in patients with stable coronary artery disease. These data might open a novel noninvasive and preventive treatment avenue for patients with non-acute vascular stenotic disease.

Impact of integrated PET/CT in the staging of oesophageal cancer: a UK population-based cohort study.

AIM: To document the impact of integrated positron-emission tomography and computed tomography (PET/CT) on the management of a cohort of UK patients undergoing PET/CT as part of their staging investigations for potentially curable oesophageal cancer. MATERIALS AND METHODS: A multicentre, prospective study of newly diagnosed patients with oesophageal cancer undergoing PET/CT was set up across five cancer networks covering a total population of 6.6 million. Data were prospectively collected for cases diagnosed between 1 November 2006 and 31 October 2007. RESULTS: One hundred and ninety-one patients underwent PET/CT, with 31 (16%) positive for possible metastatic disease. Amongst the 31 positive examinations, 18 (9.4%) were confirmed to have metastatic disease, and 13 (6.5%) patients had no subsequent evidence of metastatic disease, although in three (1.6%) of these a second previously unsuspected pathology was diagnosed. Two patients had false-negative PET/CT and were found to have metastatic disease. The results of the PET/CT examination down-staged 10 (5%) patients thought to have coeliac/M1a node involvement on CT. Fifteen of 110 (13%) patients with stage 3 or 4 disease at CT and endoscopic ultrasound (EUS) had confirmed metastatic disease at PET/CT, compared with none of 18 with stage 2b, three of 52 (6%) with stage 2a, and none of 10 with stage 1 disease. CONCLUSION: This study confirms the role of PET/CT in a multicentre UK setting in the management of patients with potentially curable carcinoma of the oesophagus, improving the accuracy of pre-treatment staging compared with CT and EUS alone. Early tumours infrequently show evidence of metastasis on PET/CT, although further data are required to confidently determine the stage of tumours where PET/CT has no additional value.

Effects of nitrous oxide on dopamine release in the rat nucleus accumbens and expectation of reward.

Recently we have shown that nitrous oxide (N2O) was able to block the expression of morphine-induced conditioned place preference (CPP) in mice. Because dopamine (DA) has also been associated with the positive place conditioning we hypothesize that exposure to N2O would be significantly associated with a modification of extracellular level of DA. Unbiased place conditioning method was used for mice and rats. Levels of DA, in the nucleus accumbens (Nac), in awake and freely moving rats during positive place conditioning after morphine chronic treatment has been measured by microdialysis. Expression of morphine-induced CPP was totally abolished in mice and rats exposed to N2O. Results of animals placed in the morphine-paired compartment showed a 75% increase in the extracellular levels of DA, which was blocked by exposure of animals to N2O. In conclusion we showed the capacity of N2O to block the expression of morphine-induced CPP in mice and in rats. Then we demonstrated an increase of DA extracellular level in the Nac when animals were placed in the morphine-paired compartment and these increase of DA level was blocked by N2O.

Hypoxia disturbs fetal hemodynamics and growth.

Low-birth-weight babies have an increased risk of cardiovascular disease (CVD) in later life. The authors hypothesize that fetal hypoxia alters the structure and function of the developing cardiovascular system resulting in CVD. They investigated the effects of chronic hypoxia on cardiac performance, hemodynamic control, and growth during the second half of embryonic chick development. Three stages of hemodynamic adaptations were identified in hypoxic chick embryos. At embryonic day 13 (E13), heart rate and blood pressure were higher in hypoxic embryos. At E17, this was followed by sympathetic hyperinnervation of peripheral arteries, resulting in increased vasoconstriction during a chemoreflex. This was accompanied by dilatation of the left ventricle and a 50% reduction in cardiac contractility. E19 hypoxic embryos had a 33% higher baseline vascular tone, but failed to maintain blood pressure during acute stress, indicating cardiac failure. Reduced body, heart, and liver weights followed the hemodynamic changes. Chronic hypoxia induces dilated cardiomyopathy and sympathetic hyperinnervation of the peripheral vasculature leading to aberrant fetal hemodynamics and fetal growth restriction. This study identifies that alterations in fetal hemodynamic regulation are in the causal pathway between disturbances in fetal environment, restricted fetal growth and CVD, and establishes fetal hypoxia as a novel risk factor for cardiovascular disease.