37 research outputs found

    Expert consensus and recommendations on safety criteria for active mobilization of mechanically ventilated critically ill adults

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    Introduction: The aim of this study was to develop consensus recommendations on safety parameters for mobilizing adult, mechanically ventilated, intensive care unit (ICU) patients. Methods: A systematic literature review was followed by a meeting of 23 multidisciplinary ICU experts to seek consensus regarding the safe mobilization of mechanically ventilated patients. Results: Safety considerations were summarized in four categories: respiratory, cardiovascular, neurological and other. Consensus was achieved on all criteria for safe mobilization, with the exception being levels of vasoactive agents. Intubation via an endotracheal tube was not a contraindication to early mobilization and a fraction of inspired oxygen less than 0.6 with a percutaneous oxygen saturation more than 90% and a respiratory rate less than 30 breaths/minute were considered safe criteria for in- and out-of-bed mobilization if there were no other contraindications. At an international meeting, 94 multidisciplinary ICU clinicians concurred with the proposed recommendations. Conclusion: Consensus recommendations regarding safety criteria for mobilization of adult, mechanically ventilated patients in the ICU have the potential to guide ICU rehabilitation whilst minimizing the risk of adverse events

    Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer.

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    BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients. RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid ( p = 0.082) and clear cell ( p = 0.083), with the most significant gene level association seen with TGFBR2 ( p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 ( p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA ( p = 0.035, endometrioid and mucinous), LGALS1 ( p = 0.03, mucinous), STAT5B ( p = 0.022, clear cell), TGFBR1 ( p = 0.021 endometrioid) and TGFBR2 ( p = 0.017 and p = 0.025, endometrioid and mucinous, respectively). CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients

    Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes

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    Several phenotypic differences observed in Parkinson’s disease (PD) patients have been linked to age at onset (AAO). We endeavoured to find out whether these differences are due to the ageing process itself by using a combined dataset of idiopathic PD (n = 430) and healthy controls (HC; n = 556) excluding carriers of known PD-linked genetic mutations in both groups. We found several significant effects of AAO on motor and non-motor symptoms in PD, but when comparing the effects of age on these symptoms with HC (using age at assessment, AAA), only positive associations of AAA with burden of motor symptoms and cognitive impairment were significantly different between PD vs HC. Furthermore, we explored a potential effect of polygenic risk score (PRS) on clinical phenotype and identified a significant inverse correlation of AAO and PRS in PD. No significant association between PRS and severity of clinical symptoms was found. We conclude that the observed non-motor phenotypic differences in PD based on AAO are largely driven by the ageing process itself and not by a specific profile of neurodegeneration linked to AAO in the idiopathic PD patients

    Exercise interventions with critically ill patients in an Australian tertiary intensive care unit

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    This thesis investigated the physical impairments experienced by critically ill patients in intensive care. Clinicians’ perceptions regarding exercise with critically ill patients were explored, and medical records analysed to illustrate that despite clinicians’ positive perceptions regarding exercise, critically ill patients rarely completed exercise interventions whilst admitted to the intensive care unit. A preliminary randomised control trial was conducted that evaluated the effectiveness of an innovative in-bed cycling intervention. In-bed cycling with critically ill patients was found to be safe, feasible and acceptable to patients, families and clinicians. Promising patient outcomes were identified that justify a future multi-centre randomised control trial

    129: Early in-bed cycling versus usual care in the ICU on muscle atrophy and mobility: a randomized trial

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    Learning Objectives: Critically ill patients lose large amounts of skeletal muscle early during their ICU admission. This muscle loss is associated with the development of weakness and functional impairments. In-bed cycling initiated early in an ICU admission may reduce muscle atrophy, maintain muscle strength and promote recovery of mobility.Methods: A two-arm (blinded assessment) randomized controlled trial (RCT) compared usual care versus early in-bed cycling (in addition to usual care). The setting was a tertiary mixed medical, surgical, trauma ICU. Participants included adult patients with expected duration of mechanical ventilation >48 hours. All participants received usual care while patients randomized to the intervention group received an additional daily intervention of 30 minutes of in-bed cycling. In-bed cycling participants were encouraged to cycle actively whenever possible whilst pre-specified safety parameters were observed. The in-bed cycling sessions could be passive, machine-assisted or active. The primary outcome was rectus femoris cross sectional area (RFCSA) measured by ultrasound (blinded ultrasonographers) at: Baseline, Days 3, 7, 10 (primary) post-study enrollment, as well as 7 days post-discharge from ICU. Other outcomes included manual muscle strength assessed by the Medical Research Council (MRC) Sum Score and distance in meters walked during the 6-minute walk test (6MWT) 7 days post-discharge from ICU.Results: Seventy-four participants (mean (SD) age = 56 (17), 69% male) were recruited. There was a difference of 4% in median RFCSA atrophy at Day 10 (primary outcome) favoring the intervention group. Participants in the in-bed cycling group (n = 37) had a median (IQR) percent of RFCSA atrophy of -9.4% (-23.2%, 0.8%) in comparison to usual care participants (n = 37) -13.2% (-26.4%, -2.9%). During the 6MWT the in-bed cycling group walked median (IQR) 258 meters (30, 326) versus usual care participants median (IQR) 210 meters (25, 318). The median (IQR) MRC Sum Score 7-days post ICU discharge was similar in the intervention 58 (54, 60) and usual care 57 (53, 59) groups.Conclusions: Outcomes following this pilot trial of daily in-bed cycling in addition to usual care were encouraging. In-bed cycling may reduce muscle atrophy and improve mobility post-critical illness. Further investigation in a larger multi-center RCT is warranted

    Usual care protein intake does not affect acute sarcopenia. Secondary analysis of an in-bed cycling trial with critical ill patients

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    Introduction: Critically ill patients typically experience profound acute skeletal muscle loss. The associations between exercise interventions and protein intake to preserve skeletal muscle are unknown.Objectives: The objectives were to: i) examine the associations between protein intake and acute muscle loss; ii) examine whether in-bed cycling affected muscle loss when adjusted for protein received; iii) determine if identifiable patient characteristics can predict which patients are most likely to experience profound muscle loss.Methods: A secondary analysis using a mixed effects model of a randomised clinical trial examined the associations between protein intake and acute muscle loss, defined as rectus femoris cross-sectional area (RFCSA) decrease per day. Patients received usual care nutritional intake while in intensive care.Results: Eligible participants (n=72) enrolled in the Critical Care In-bed Cycling Study (mean(SD) age, 56(17) years; male(69%) were analysed. Patients received a mean(SD) of 59%(26) of the minimum protein dose recommended for critically ill patients. Results indicated that patients’ RFCSA decreased over time (Estimate =-0.04, 95%CI:-0.08 to -0.01). Patients with higher modified nutrition risk scores (mNUTRIC) lost more RFCSA over time (Estimate=-0.41; 95% CI:-0.59 to -0.23). Cycling group allocation (Estimate=-0.59, 95%CI:-1.53 to 0.34), the percentage of protein requirements received (Estimate=-0.48; 95%CI:-1.16 to 0.19), did not share a statistically significant association with RFCSA.Conclusion(s): Patients with a higher mNUTRIC scores are at the greatest risk of acute muscle loss and could be the focus of future rehabilitation and nutritional interventions. In this small, single centre trial, we could not demonstrate any impact of protein intake or cycling on muscle mass. The lower than recommended protein intake observed in the present study may have contributed to loss of RFCSA observed and limited benefit that was derived from the in-bed cycling exercise intervention
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