Assessing the quality of cardiac rehabilitation programs by measuring adherence to the Australian quality indicators.

BACKGROUND: Every year, over 65,000 Australians experience an acute coronary syndrome (ACS) and around one-third occur in people with prior coronary heart disease. Cardiac rehabilitation (CR) aims to prevent a repeat ACS by supporting patients' return to an active and fulfilling lifestyle. CR programs are efficacious, but audits of clinical practice show variability of program delivery, which may compromise patient outcomes. Core components, quality indicators and accreditation of programs have been introduced internationally to increase program standardisation. With Australian quality indicators (QIs) for cardiac rehabilitation recently introduced, we aimed to conduct a survey in one state of Australia to assess the extent to which programs adhere to the measurement of QIs comparing country, metropolitan, telephone and face to face programs. METHODS: A cross- sectional survey design with face validity testing was used to formulate questions to evaluate cardiac rehabilitation program and personnel characteristics and QI adherence. Between October 2020- December 2021, 23 cardiac rehabilitation programs across country and metropolitan areas were invited to participate. Quality improvement was defined as adherence to the Australian Quality Indicators, and we developed an objective score to calculate program performance categorised by quartiles. Significance of CR completion and time to enrolment between program type (telephone versus face to face) and location (country versus metropolitan were compared using Pearson's Chi-square and Mann-Whitney U tests. RESULTS: Among the 23 CR programs, 15 were country and 8 metropolitan-based and 22 were face to face and 1 telephone-based. Median wait time from discharge was 27.0 days, (interquartile range 19.3-46.0) across all programs and country completions of enrolled were 76.9% versus metropolitan 56.5%, p < 0.001 and telephone versus face to face 92.9% versus 59.6% p < 0.001. Pre-program QI adherence was higher than post program for depression, medication adherence, health-related quality of life and comprehensive re-assessment. Seventy four percent of programs were ranked at a medium level of performance (mean score: 11.4/16, SD ± 0.79). CONCLUSIONS: A survey of 23 cardiac rehabilitation programs, showed variability in adherence to measurement of the Australian Cardiovascular and Rehabilitation Association and Australian Heart Foundation Cardiac Rehabilitation Quality Indicators. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry (ANZCTR), ACTRN12621000222842 , registered 03/03/2021.

Does hospital design impact on patient activity levels and time spent alone?

PURPOSE: The aim of this study was to quantify changes in patients' activity levels, location and people present, within one acute stroke unit (ASU) and one inpatient rehabilitation unit (IRU) with respect to change in hospital design. METHODS: A prospective observational study using behavioural mapping. We observed participants from 8 am till 5 pm every 10 minutes across two days and compared participant activity (physical, social and cognitive), location and people present pre and post-transition to new units. Built design, staffing levels and models of care were contrasted. RESULTS: We recruited 73 participants (63% stroke): old-ASU (n = 19); new-ASU (n = 15); old-IRU (n = 19); new-IRU (n = 20). Compared to old, new units had more single rooms, larger floor spaces and higher staffing levels. We found no significant change in participants' activity levels between the old and new ASU. Participants in the new IRU showed increased physical activity (43.4% vs. 54.4%, p = 0.02) but social and cognitive activity remained similar. Participants were more alone (ASU 47.4% vs. 66.7%, p = 0.01; IRU 41.7% vs. 58.3%, p < 0.001), and less often with nursing staff (ASU 17.7% vs. 6.7%, p = 0.04; IRU 18.8% vs. 5.7%, p < 0.001) in new units. CONCLUSION: Hospital design appears to impact on patients' physical activity. Single rooms may increase isolation and reduce interaction with nursing staff.Implications for rehabilitationDesign of new rehabilitation units needs to consider patients' social engagement with family, friends, other patients and staff in addition to privacy and infection control.A change in built design of rehabilitation units should prompt observation of patients' activity levels and engagement with people and available space to ensure optimal use of new environments.Promotion of communal spaces and activities away from the bedroom to encourage social engagement is recommended for patients recovering in rehabilitation facilities.Less time in contact with nursing staff in rehabilitation environments with predominantly single rooms suggests a review of clinical practice and patient safety is warranted.

New tuberculosis vaccines: advances in clinical development and modelling.

Tuberculosis remains a major source of morbidity and mortality worldwide, with 10 million cases and 1.5 million deaths in 2018. Achieving 'End TB' prevention and care goals by 2035 will likely require a new tuberculosis vaccine. The tuberculosis vaccine development pipeline has seen encouraging progress; however, questions around their population impact and implementation remain. Mathematical modelling investigates these questions to inform vaccine development and deployment strategies. We provide an update on the current vaccine development pipeline, and a systematic literature review of mathematical modelling of the epidemiological impact of new tuberculosis vaccines. Fourteen prophylactic tuberculosis vaccine candidates are currently in clinical trials. Two candidates have shown promise in phase II proof-of-concept efficacy trials: M72/AS01E demonstrated 49.7% (95% CI; 2.1, 74.2) protection against tuberculosis disease, and BCG revaccination demonstrated 45.4% (95% CI; 6.4, 68.1) protection against sustained Mycobacterium tuberculosis infection. Since the last modelling review, new studies have investigated the epidemiological impact of differential vaccine characteristics, age targeting and spatial/risk group targeting. Critical research priorities for M72/AS01E include completing the currently in-design trial, powered to improve the precision of efficacy estimates, include uninfected populations and further assess safety and immunogenicity in HIV-infected people. For BCG revaccination, the priority is completing the ongoing confirmation of efficacy trial. Critical modelling gaps remain on the full value proposition of vaccines, comparisons with other interventions and more realistic implementation strategies. Using carefully designed trials and modelling, we must prepare for success, to ensure that new vaccines will be promptly received by those most in need.

INTU is essential for oncogenic Hh signaling through regulating primary cilia formation in basal cell carcinoma.

Inturned (INTU), a cilia and planar polarity effector, performs prominent ciliogenic functions during morphogenesis, such as in the skin. INTU is expressed in adult tissues but its role in tissue maintenance is unknown. Here, we report that the expression of the INTU gene is aberrantly elevated in human basal cell carcinoma (BCC), coinciding with increased primary cilia formation and activated hedgehog (Hh) signaling. Disrupting Intu in an oncogenic mutant Smo (SmoM2)-driven BCC mouse model prevented the formation of BCC through suppressing primary cilia formation and Hh signaling, suggesting that Intu performs a permissive role during BCC formation. INTU is essential for intraflagellar transport A complex assembly during ciliogenesis. To further determine whether Intu is directly involved in the activation of Hh signaling downstream of ciliogenesis, we examined the Hh signaling pathway in mouse embryonic fibroblasts, which readily responds to the Hh pathway activation. Depleting Intu blocked Smo agonist-induced Hh pathway activation, whereas the expression of Gli2ΔN, a constitutively active Gli2, restored Hh pathway activation in Intu-deficient cells, suggesting that INTU functions upstream of Gli2 activation. In contrast, overexpressing Intu did not promote ciliogenesis or Hh signaling. Taken together, data obtained from this study suggest that INTU is indispensable during BCC tumorigenesis and that its aberrant upregulation is likely a prerequisite for primary cilia formation during Hh-dependent tumorigenesis.

A meta-analysis of sperm donation offspring health outcomes.

Although the use of donor sperm as a treatment modality for male infertility has become common place, the health outcomes for those conceived has been poorly studied. A structured search of the literature using PubMed, EMBASE and Cochrane Reviews was performed to investigate the health outcomes of offspring conceived from donor sperm. Eight studies were eligible and included in the review, and of these, three were included in a meta-analysis. Meta-analysis of clinical outcomes showed that donor sperm neonates are not at increased risk of being born of low birth weight (<2500 g), preterm (<37 weeks) or with increased incidences of birth defects, than spontaneously conceived neonates.

Standing balance post total knee arthroplasty: sensitivity to change analysis from four to twelve weeks in 466 patients.

OBJECTIVE: Little is known about how static standing balance changes post total knee arthroplasty (TKA). The primary aim of this study was to examine the sensitivity to change and redundancy of center of pressure (COP) variables post-TKA. The secondary aim was to compare the sensitivity of these measures to standard clinical assessments of one repetition maximum knee extension strength and fast pace gait speed. DESIGN: 466 participants performed instrumented double-limb standing balance tests with eyes open at 4 and 12 weeks post-TKA. Measures of COP standard deviation, amplitude, root mean square (RMS), path length, detrended fluctuation analysis (DFA) and signal frequency content for the medial-lateral (ML) and anterior-posterior (AP) axes were examined. RESULTS: Significant decreases in total path length, ML variables related to sway velocity and AP signal complexity and frequency were observed. Inter-session Cohen's d effect size (ES) revealed the strongest effect was for high velocity ML path length, with a 12% decrease in this rapid sway. This variable, along with AP mean instantaneous frequency and AP DFA, were the only ones significantly different with effect sizes >0.20 and non-redundant (Spearman's rho <0.75). The ES of COP-derived variables (maximum = 0.45) were lower than gait speed (1.40) and knee extensor strength (1.54). CONCLUSION: Increased high velocity ML sway is present at four compared to 12 weeks post-TKA. This augmented rapid sway may provide increased challenges to the postural control system at a time coinciding with reduced strength levels, which could have implications for physical function during activities of daily living.

Immediate tangential excision accelerates wound closure but does not reduce scarring of mid-dermal porcine burns.

Current evidence supports the use of excision to remove eschar from deep dermal and full-thickness burns. However, the role of excision of mid-dermal burns remains unclear. This study aimed to develop a porcine model that could produce reproducible middermal thermal burns that undergo tangential excision; and investigate the effects of immediate tangential excision (30 minutes postburn) on healing and scarring. An aluminum bar preheated in hot water (70°C) was applied for 20 or 30 s to produce a total of sixteen mid-dermal burns per pig on each of six pigs. Thirty minutes after burn creation, half of the burns were tangentially excised. Four partial- thickness wounds per pig were created as controls. Depth of burn injury (1 and 24 h), reepithelialization (7 and 10 d) and scar depth (28 d) were assessed microscopically. Total scar surface area was grossly evaluated on day 28. Exposure of porcine skin to a preheated aluminum bar at 70 °C for 20 or 30 sec resulted in reproducible mid-dermal burns, where immediate excision enhanced complete wound closure as judged by complete re-epithelialization, but did not reduce initial depth of injury, scar contraction and scar depth. Immediate surgical intervention is sufficient to enhance wound closure, but not to mitigate mid-dermal burn scar formation. This work provides a suitable animal model to evaluate novel therapies that may be used to inhibit burn progression, accelerate wound closure and decrease scarring, especially those therapies unable to penetrate burn eschar.

Les données actuelles des connaissances sont en faveur de l'excision des brûlures des 2ème degré profond et 3ème degré. L'intérêt de l'excision des brûlures intermédiaires reste mal précisé. Cette étude se penche sur un modèle porcin destiné à la réalisation de brûlures intermédiaires reproductibles et à l'évaluation de l'effet l'excision ultra précoce (30 mn après la brûlure) sur l'épidermisation et la cicatrisation de ces brûlures. Six porcs ont subi chacun un total de 16 brûlures intermédiaires infligées au moyen d'une barre d'aluminium chauffée à 70°C et appliquée pendant 20 à 30 s. La moitié des zones brûlées étaient excisées à la trentième minute. Quatre brûlures superficielles servaient de contrôle. La profondeur de la brûlure (à h1 et h24), la réépithélialisation (à J7 et J10) et l'épaisseur de la cicatrice (à J28), étaient étudiées microscopiquement. La surface cicatricielle totale était évaluée à J28. L'exposition pendant 20 à 30s de la peau d'un porc à de l'aluminium préalablement chauffé à 70°C entraîne une brûlure intermédiaire reproductible. L'excision immédiate en favorise la guérison lorsqu'elle est jugée sur la réépithélialisation mais n'en réduit ni la profondeur, ni la rétraction cicatricielle, pas plus que l'épaisseur de la cicatrice. L'excision immédiate favorise la fermeture de la plaie mais pas son évolution vers des séquelles. Ce travail permet de décrire un modèle animal fiable dans le but d'évaluer de nouvelles thérapeutiques destinées à limiter le progression des lésions, accélérer la fermeture et diminuer la survenues de séquelles, en particulier celles incapables de pénétrer dans une lésion constituée.

Heart failure following cancer treatment: characteristics, survival and mortality of a linked health data analysis.

BACKGROUND: Cardiotoxicity resulting in heart failure is a devastating complication of cancer therapy. A patient may survive cancer only to develop heart failure (HF), which has a higher mortality rate than some cancers. AIM: This study aimed to describe the characteristics and outcomes of HF in patients with blood or breast cancer after chemotherapy treatment. METHODS: Queensland Cancer Registry, Death Registry and Hospital Administration records were linked (1996-2009). Patients were categorised as those with an index HF admission (that occurred after cancer diagnosis) and those without an index HF admission (non-HF). RESULTS: A total of 15 987 patients was included, and 1062 (6.6%) had an index HF admission. Median age of HF patients was 67 years (interquartile range 58-75) versus 54 years (interquartile range 44-64) for non-HF patients. More men than women developed HF (48.6% vs 29.5%), and a greater proportion in the HF group had haematological cancer (83.1%) compared with breast cancer (16.9%). After covariate adjustment, HF patients had increased mortality risk compared with non-HF patients (hazard ratios 1.67 (95% confidence interval, 1.54-1.81)), and 47% of the index HF admission occurred within 1 year from cancer diagnosis and 70% within 3 years. CONCLUSION: Cancer treatment may place patients at a greater risk of developing HF. The onset of HF occurred soon after chemotherapy, and those who developed HF had a greater mortality risk.

Novel application of high-dose rate brachytherapy for severe, recalcitrant palmoplantar pustulosis.

Palmoplantar pustulosis (PPP) is a chronic pustular dermatitis of the palms and soles, which is frequently associated with significant pruritus and pain, often limiting daily activities. We present the case of a 36-year-old man with severe PPP who had treatment failure with multiple medical therapies but showed marked improvement with high-dose rate brachytherapy. Brachytherapy has the advantage of providing a conformal dose distribution over complex curved surfaces, such as the foot and ankle. Our observations suggest that brachytherapy may be a well-tolerated treatment option for patients with severe, refractory PPP.

Codominant Role of Interferon-γ- and Interleukin-17-Producing T Cells During Rejection in Full Facial Transplant Recipients.

Facial transplantation is a life-changing procedure for patients with severe composite facial defects. However, skin is the most immunogenic of all transplants, and better understanding of the immunological processes after facial transplantation is of paramount importance. Here, we describe six patients who underwent full facial transplantation at our institution, with a mean follow-up of 2.7 years. Seum, peripheral blood mononuclear cells, and skin biopsy specimens were collected prospectively, and a detailed characterization of their immune response (51 time points) was performed, defining 47 immune cell subsets, 24 serum cytokines, anti-HLA antibodies, and donor alloreactivity on each sample, producing 4269 data points. In a nonrejecting state, patients had a predominant T helper 2 cell phenotype in the blood. All patients developed at least one episode of acute cellular rejection, which was characterized by increases in interferon-γ/interleukin-17-producing cells in peripheral blood and in the allograft's skin. Serum monocyte chemotactic protein-1 level was significantly increased during rejection compared with prerejection time points. None of the patients developed de novo donor-specific antibodies, despite a fourfold expansion in T follicular helper cells at 1 year posttransplantation. In sum, facial transplantation is frequently complicated by a codominant interferon-γ/interleukin-17-mediated acute cellular rejection process. Despite that, medium-term outcomes are promising with no evidence of de novo donor-specific antibody development.

Early changes in Achilles tendon behaviour in vivo following downhill backwards walking.

Downhill backwards walking causes repeated, cyclical loading of the muscle-tendon unit. The effect this type of repeated loading has on the mechanical behaviour of the Achilles tendon is presently unknown. This study aimed to investigate the biomechanical response of the Achilles tendon aponeurosis complex following a downhill backwards walking protocol. Twenty active males (age: 22.3 ± 3.0 years; mass: 74.7 ± 5.6 kg; height: 1.8 ± 0.7 m) performed 60 min of downhill (8.5°), backwards walking on a treadmill at -0.67 m · s(-1). Data were collected before, immediately post, and 24-, 48- and 168-h post-downhill backwards walking. Achilles tendon aponeurosis elongation, strain and stiffness were measured using ultrasonography. Muscle force decreased immediately post-downhill backward walking (P = 0.019). There were increases in Achilles tendon aponeurosis stiffness at 24-h post-downhill backward walking (307 ± 179.6 N · mm(-1), P = 0.004), and decreases in Achilles tendon aponeurosis strain during maximum voluntary contraction at 24 (3.8 ± 1.7%, P = 0.008) and 48 h (3.9 ± 1.8%, P = 0.002) post. Repeated cyclical loading of downhill backwards walking affects the behaviour of the muscle-tendon unit, most likely by altering muscle compliance, and these changes result in tendon stiffness increases.

A meta-analysis of neonatal health outcomes from oocyte donation.

Donated oocytes are a treatment modality for female infertility which is also associated with increased risks of preeclampsia. Subsequently it is important to evaluate if there is concomitant increased risks for adverse neonatal events in donated oocyte neonates. A structured search of the literature using PubMed, EMBASE and Cochrane Reviews was performed to investigate the perinatal health outcomes of offspring conceived from donor oocytes compared with autologous oocytes. Meta-analysis was performed on comparable outcomes data. Twenty-eight studies were eligible and included in the review, and of these, 23 were included in a meta-analysis. Donor oocyte neonates are at increased risk of being born with low birth weight (<2500 g) [risk ratio (RR): 1.18, 95% confidence interval (CI): 1.14-1.22, P-value (P)<0.00001], very low birth weight (<1500 g) (RR: 1.24, CI: 1.15-1.35, P<0.00001), preterm (<37 weeks) (RR: 1.26, CI: 1.23-1.30, P<0.00001), of lower gestational age (mean difference -0.3 weeks, CI: -0.35 weeks to -0.25 weeks, P<0.00001), and preterm with low birth weight (RR: 1.24, CI: 1.19-1.29, P<0.00001), when compared with autologous oocyte neonates. Conversely, low birth weight outcomes were improved in term donor oocyte neonates (RR: 0.86, CI: 0.8-0.93, P=0.0003). These negative outcomes remained significant when controlling for multiple deliveries. The donor oocyte risk rates are higher than those found in general ART outcomes, are important considerations for the counselling of infertile patients and may also influence the long term health of the offspring.

Hematopoietic knockdown of PPARδ reduces atherosclerosis in LDLR-/- mice.

PPARδ (peroxisome proliferator-activated receptor δ) mediates inflammation in response to lipid accumulation. Systemic administration of a PPARδ agonist can ameliorate atherosclerosis. Paradoxically, genetic deletion of PPARδ in hematopoietic cells led to a reduction of atherosclerosis in murine models, suggesting that downregulation of PPARδ expression in these cells may mitigate atherogenesis. To advance this finding forward to potential clinical translation through hematopoietic stem cell transplantation-based gene therapy, we employed a microRNA (miRNA) approach to knock down PPARδ expression in bone marrow cells followed by transplantation of the cells into LDLR-/- mice. We found that knockdown of PPARδ expression in the hematopoietic system caused a dramatic reduction in aortic atherosclerotic lesions. In macrophages, a key component in atherogenesis, knockdown of PPARδ led to decreased expression of multiple pro-inflammatory factors, including monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-1ß and IL-6. Expression of CCR2, a receptor for MCP-1, was also decreased. The downregulation of pro-inflammatory factors is consistent with significant reduction of macrophage presence in the lesions, which may also be attributable to elevation of ABCA1 (ATP-binding cassette, subfamily A, member 1) and depression of adipocyte differentiate-related protein. Furthermore, the abundance of both MCP-1 and matrix metalloproteinase-9 proteins was reduced in plaque areas. Our results demonstrate that miRNA-mediated PPARδ knockdown in hematopoietic cells is able to ameliorate atherosclerosis.

Associations of calf inter- and intra-muscular adipose tissue with cardiometabolic health and physical function in community-dwelling older adults.

OBJECTIVES: To determine associations of inter- and intra-muscular adipose tissue (IMAT) with cardiometabolic health and physical function in older adults. METHODS: 48 community-dwelling older adults aged ⋝65 years (mean 71.6±4.8 years; 52% women) underwent whole-body dual-energy X-ray absorptiometry, to assess appendicular lean mass (ALM), and peripheral quantitative computed tomography (pQCT; 66% tibia), to assess calf IMAT cross-sectional area ([CSA]; cm2) and muscle density (mg/cm(3); higher values indicate lower fat infiltration). Fasting glucose, lipids, triglycerides and C-reactive protein (CRP) were analysed. Physical function was assessed by postural sway (computerised posturography; N=41), and gait analysis (GAITRite Electronic Walkway; N=40). RESULTS: Higher IMAT CSA and muscle density were associated with significantly higher (B=0.85 95%CI [0.34, 1.36]) and lower (-2.14 [-4.20, -0.08]) CRP and higher (0.93 [0.56, 1.30]) and lower postural sway (-3.12 [-4.74, -1.50]), respectively, after adjustment for age, sex and ALM/BMI. Higher IMAT CSA was associated with slower gait speed and cadence, and greater step time and step width (all P<0.03), while higher muscle density was associated with smaller step width (P<0.01) only. CONCLUSIONS: Older adults with higher calf IMAT have poorer balance, mobility and inflammatory status. Interventions aimed at improving physical function in older adults should incorporate strategies to reduce IMAT.

Mycoplasma genitalium infection among HIV-positive women: prevalence, risk factors and association with vaginal shedding.

This study examined the prevalence and factors associated with Mycoplasma genitalium (MG) infection among HIV-positive women and the association between MG and vaginal HIV-1 RNA shedding. HIV-positive women attending an outpatient clinic in New Orleans, Louisiana, USA, from 2002 to 2005 were examined for a battery of sexually transmitted infections (STIs) and underwent a behavioural survey. A selected subset had a measurement of vaginal shedding analysed. Of the 324 HIV-positive women, 32 (9.9%) were infected with MG. HIV-positive women with MG were more likely to be co-infected with Neisseria gonorrhoeae and Chlamydia trachomatis and to have had ≥1 male sexual partners in the last month. In the subset (n = 164), no differences were found in the presence of detectable vaginal HIV-1 RNA between women infected and not infected with MG (30.8% versus 34.8% shedding; P = 0.69). While MG was a common co-STI in this sample of HIV-positive women, it was not associated with vaginal HIV shedding.

Macrophage LXRα gene therapy ameliorates atherosclerosis as well as hypertriglyceridemia in LDLR(-/-) mice.

Liver X receptors (LXRs) are implicated in the regulation of cholesterol homeostasis, inflammatory response and atherogenesis. Administration of LXR agonists inhibits the progress of atherosclerosis, and also increases plasma triglyceride levels, representing an obstacle to their use in treating this disease. The objective of this study was to develop an alternative approach that could overcome this obstacle. Eight-week-old low-density lipoprotein receptor-deficient (LDLR(-/-)) mice were transplanted with hematopoietic stem cell (HSC)-enriched bone marrow cells transduced with lentivectors expressing either green fluorescent protein (GFP) (Lenti-SP-GFP, control) or LXRα (Lenti-SP-LXRα) driven by a synthetic macrophage promoter. At 4 weeks post-transplant, the mice were fed with a Western diet for 8 weeks and then killed. Compared with Lenti-SP-GFP mice, the Lenti-SP-LXRα mice had a 30% reduction in atherosclerotic lesions, which was accompanied by increases in levels of macrophage expression of cholesterol efflux genes apolipoprotein E and ATP-binding cassette A1, as well as decreases in plasma inflammatory cytokines interleukin-6 and tumor necrosis factor-α. Intriguingly, a 50% reduction of plasma triglyceride level was also observed. We conclude that HSC-based macrophage LXRα gene therapy ameliorates the development of atherosclerosis along with an unexpected concomitant reduction of plasma triglyceride levels in LDLR(-/-) mice. These findings highlight the potential value of macrophage LXR expression as an avenue for therapeutic intervention against atherosclerosis.