Objectives: To develop a comprehensive set of items describing physiotherapy mobilisation practices for critically ill patients, and to document current practices in intensive care units in Australia ...and New Zealand, focusing on patients having > 48 hours of mechanical ventilation. Design: Prospective, observational, multicentre, single-day, point prevalence study. Participants and setting: All patients in 38 Australian and New Zealand ICUs at 10 am on one of three designated days in 2009 and 2010. Main outcome measures: Demographic data, admission diagnosis and mobilisation practices that had occurred in the previous 24 hours. Results: 514 patients were enrolled, with 498 complete datasets. Mean age was 59.2 years (SD, 16.7 years) and 45% were mechanically ventilated. Mobilisation activities were classified into five categories that were not mutually exclusive: 140 patients (28%) completed an in-bed exercise regimen, 93 (19%) sat over the side of the bed, 182 (37%) sat out of bed, 124 (25%) stood and 89 (18%) walked. Predefined adverse events occurred on 24 occasions (5%). No patient requiring mechanical ventilation sat out of bed or walked. On the study day, 391 patients had been in ICU for > 48 hours. There were 384 complete datasets available for analysis and, of these, 332 patients (86%) were not walked. Of those not walked, 76 (23%) were in the ICU for >=7 days. Conclusion: Patient mobilisation was shown to be low in a single-day point prevalence study. Future observational studies are required to confirm the results.
Background:
Physical rehabilitation can benefit critically ill patients during intensive care unit (ICU) admission, but routine clinical practice remains inconsistent nor examined in prolonged ...mechanical ventilation patients transferred to a specialist ventilator weaning unit (VWU). Behavioral mapping is a sampling approach that allows detailed reporting of physical activity profiles. The objective of this study was to characterize the physical activity profile of critically ill patients in a UK ICU and VWU.
Methods:
Single-center, prospective observational study in a university teaching hospital. Patient observations, conducted Monday through Sunday from 08:30 am to 08:00 pm and for 1 minute every 10 minutes, included data points of patient location, people in attendance, and highest level of activity. Descriptive statistics were utilized to analyze and report data.
Results:
Forty-two ICU and 11 VWU patients were recruited, with 2646 and 693 observations, respectively, recorded. In the ICU, patients spent a median (interquartile range) of 100% (96%-100%) of the day (10.5 10.0-10.5 hours) located in bed, with minimal/no activity for 99% (96%-100%) of the day (10.4 9.7-10.5 hours). Nursing staff were most frequently observed in attendance with patients irrespective of ventilation or sedation status, although patients still spent approximately two-thirds of the day alone. Bed-to-chair transfer was the highest activity level observed. In the VWU, patients spent 94% (73%-100%) of the day (9.9 7.7-10.5 hours) in bed and 56% (43%-60%) of time alone. Physical activity levels were higher and included ambulation. All physical activities occurred during physical rehabilitation sessions.
Conclusions:
These profiles of low physical activity behavior across both patients in the ICU and VWU highlight the need for targeted strategies to improve levels beyond therapeutic rehabilitation and support for a culture shift toward providing patients with, and engaging them in, a multidisciplinary, multiprofessional environment that optimizes overall physical activity.
Abstract Purpose Critical illness can result in impaired physical function. Increased physical activity, additional to rehabilitation, has demonstrated improved functional independence at hospital ...discharge. The purpose of this study was to measure patterns of physical activity in a group of critically ill patients. Methods This was a single-center, open, observational behavioral mapping study performed in a quaternary intensive care unit (ICU) in Melbourne, Australia. Observations were collected every 10 minutes for 8 hours between 8:00 am and 5:00 pm with the highest level of physical activity, patient location, and persons present at the bedside recorded. Results Two thousand fifty observations were collected across 8 days. Patients spent more than 7 hours in bed (median interquartile range of 100% 69%-100%) participating in little or no activity for approximately 7 hours of the day (median interquartile range 96% 76%-96%). Outside rehabilitation, no activities associated with ambulation were undertaken. Patients who were ventilated at the time of observation compared with those who were not were less likely to be out of bed (98% reduction in odds). Patients spent up to 30% of their time alone. Conclusion Outside rehabilitation, patients in ICU are inactive and spend approximately one-third of the 8-hour day alone. Strategies to increase physical activity levels in ICU are required.
Background: Case-based learning (CBL) is an established pedagogical active learning method used in various disciplines and defined based on the field of study and type of case. The utility of CBL for ...teaching specific aspects of cancer diagnosis to practising pathologists has not been previously studied in sub-Saharan Africa.Objectives: We aimed to pilot test standardised cancer cases on a group of practising pathologists in sub-Saharan Africa to evaluate case content, clarity of questions and delivery of content.Methods: Expert faculty created cases for the four most commonly diagnosed cancers. The format included mini-cases and bullet cases which were all open-ended. The questions dealt with interpretation of clinical information, gross specimen examination, morphologic characteristics of tumours, ancillary testing, reporting and appropriate communication to clinicians.Results: Cases on breast, cervical, prostate and colorectal cancers were tested on seven practising pathologists. Each case took an average of 45–90 min to complete.Questions that were particularly challenging to testers were on:• Specimens they should have been but for some reason were not exposed to in routine practice.• Ancillary testing and appropriate tumour staging.New knowledge gained included tumour grading and assessment of radial margins. Revisions to cases were made based on testers’ feedback, which included rewording of questions to reduce ambiguity and adding of tables to clarify concepts.Conclusion: Cases were created for CBL in Kenya, but these are applicable elsewhere in Africa and beyond to teach cancer diagnosis. The pilot testing of cases prepared faculty for the actual CBL course and feedback provided by the testers assisted in improving the questions and impact on day-to-day practice.
Ionizing radiation is a potent carcinogen, inducing cancer through DNA damage. The signatures of mutations arising in human tissues following in vivo exposure to ionizing radiation have not been ...documented. Here, we searched for signatures of ionizing radiation in 12 radiation-associated second malignancies of different tumour types. Two signatures of somatic mutation characterize ionizing radiation exposure irrespective of tumour type. Compared with 319 radiation-naive tumours, radiation-associated tumours carry a median extra 201 deletions genome-wide, sized 1-100 base pairs often with microhomology at the junction. Unlike deletions of radiation-naive tumours, these show no variation in density across the genome or correlation with sequence context, replication timing or chromatin structure. Furthermore, we observe a significant increase in balanced inversions in radiation-associated tumours. Both small deletions and inversions generate driver mutations. Thus, ionizing radiation generates distinctive mutational signatures that explain its carcinogenic potential.
Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and ...communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including
CADM2
,
ABHD14A
,
CHRFAM7A
,
GRIK2
,
GRM3
,
EPHA3
,
FGF10
,
KCND2
,
PDZK1, IMMP2L
and
FOXP2
. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios
.
Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
BackgroundAutism spectrum disorder (ASD) is characterised by impairments in social communication and by a pattern of repetitive behaviours, with learning disability (LD) typically seen in up to 70% ...of cases. A recent study using the PPL statistical framework identified a novel region of genetic linkage on chromosome 16q21 that is limited to ASD families with LD.MethodsIn this study, two families with autism and/or LD are described which harbour rare >1.6 Mb microdeletions located within this linkage region. The deletion breakpoints are mapped at base-pair resolution and segregation analysis is performed using a combination of 1M single nucleotide polymorphism (SNP) technology, array comparative genomic hybridisation (CGH), long-range PCR, and Sanger sequencing. The frequency of similar genomic variants in control subjects is determined through analysis of published SNP array data. Expression of CDH8, the only gene disrupted by these microdeletions, is assessed using reverse transcriptase PCR and in situ hybridisation analysis of 9 week human embryos.ResultsThe deletion of chr16: 60 025 584–61 667 839 was transmitted to three of three boys with autism and LD and none of four unaffected siblings, from their unaffected mother. In a second family, an overlapping deletion of chr16: 58 724 527–60 547 472 was transmitted to an individual with severe LD from his father with moderate LD. No copy number variations (CNVs) disrupting CDH8 were observed in 5023 controls. Expression analysis indicates that the two CDH8 isoforms are present in the developing human cortex.ConclusionRare familial 16q21 microdeletions and expression analysis implicate CDH8 in susceptibility to autism and LD.
While the highly consistent gene order and axial colinear patterns of expression seem to be a feature of vertebrate hox gene clusters, this pattern may be less well conserved across the rest of the ...bilaterians. We report the first deuterostome instance of an intact hox cluster with a unique gene order where the paralog groups are not expressed in a sequential manner. The finished sequence from BAC clones from the genome of the sea urchin, Strongylocentrotus purpuratus, reveals a gene order wherein the anterior genes (Hox1, Hox2 and Hox3) lie nearest the posterior genes in the cluster such that the most 3' gene is Hox5. (The gene order is 5'-Hox1, 2, 3, 11/13c, 11/13b, 11/13a, 9/10, 8, 7, 6, 5-3'.) The finished sequence result is corroborated by restriction mapping evidence and BAC-end scaffold analyses. Comparisons with a putative ancestral deuterostome Hox gene cluster suggest that the rearrangements leading to the sea urchin gene order were many and complex.
Critical illness requiring invasive mechanical ventilation can precipitate important functional disability, contributing to multidimensional morbidity following admission to an intensive care unit ...(ICU). Early in-bed cycle ergometry added to usual physiotherapy may mitigate ICU-acquired physical function impairment.BACKGROUNDCritical illness requiring invasive mechanical ventilation can precipitate important functional disability, contributing to multidimensional morbidity following admission to an intensive care unit (ICU). Early in-bed cycle ergometry added to usual physiotherapy may mitigate ICU-acquired physical function impairment.We randomly assigned 360 adult ICU patients undergoing invasive mechanical ventilation to receive 30 minutes of early in-bed Cycling + Usual physiotherapy (n=178) or Usual physiotherapy alone (n=182). The primary outcome was the Physical Function ICU Test-scored (PFIT-s) at 3 days after discharge from the ICU (the score ranges from 0 to 10, with higher scores indicating better function).METHODSWe randomly assigned 360 adult ICU patients undergoing invasive mechanical ventilation to receive 30 minutes of early in-bed Cycling + Usual physiotherapy (n=178) or Usual physiotherapy alone (n=182). The primary outcome was the Physical Function ICU Test-scored (PFIT-s) at 3 days after discharge from the ICU (the score ranges from 0 to 10, with higher scores indicating better function).Cycling began within a median (interquartile range) of 2 (1 to 3) days of starting mechanical ventilation; patients received 3 (2 to 5) cycling sessions for a mean (±standard deviation) of 27.2 ± 6.6 minutes. In both groups, patients started Usual physiotherapy within 2 (2 to 4) days of mechanical ventilation and received 4 (2 to 7) Usual physiotherapy sessions. The duration of Usual physiotherapy was 23.7 ± 15.1 minutes in the Cycling + Usual physiotherapy group and 29.1 ± 13.2 minutes in the Usual physiotherapy group. No serious adverse events occurred in either group. Among survivors, the PFIT-s at 3 days after discharge from the ICU was 7.7 ± 1.7 in the Cycling + Usual physiotherapy group and 7.5 ± 1.7 in the Usual physiotherapy group (absolute difference, 0.23 points; 95% confidence interval, -0.19 to 0.65; P=0.29).RESULTSCycling began within a median (interquartile range) of 2 (1 to 3) days of starting mechanical ventilation; patients received 3 (2 to 5) cycling sessions for a mean (±standard deviation) of 27.2 ± 6.6 minutes. In both groups, patients started Usual physiotherapy within 2 (2 to 4) days of mechanical ventilation and received 4 (2 to 7) Usual physiotherapy sessions. The duration of Usual physiotherapy was 23.7 ± 15.1 minutes in the Cycling + Usual physiotherapy group and 29.1 ± 13.2 minutes in the Usual physiotherapy group. No serious adverse events occurred in either group. Among survivors, the PFIT-s at 3 days after discharge from the ICU was 7.7 ± 1.7 in the Cycling + Usual physiotherapy group and 7.5 ± 1.7 in the Usual physiotherapy group (absolute difference, 0.23 points; 95% confidence interval, -0.19 to 0.65; P=0.29).Among adults receiving mechanical ventilation in the ICU, adding early in-bed Cycling to usual physiotherapy did not improve physical function at 3 days after discharge from the ICU compared with Usual physiotherapy alone. Cycling did not cause any serious adverse events. (Funded by the Canadian Institutes of Health Research and others; ClinicalTrials.gov numbers, NCT03471247 full randomized clinical trial and NCT02377830 CYCLE Vanguard 46-patient internal pilot.).CONCLUSIONSAmong adults receiving mechanical ventilation in the ICU, adding early in-bed Cycling to usual physiotherapy did not improve physical function at 3 days after discharge from the ICU compared with Usual physiotherapy alone. Cycling did not cause any serious adverse events. (Funded by the Canadian Institutes of Health Research and others; ClinicalTrials.gov numbers, NCT03471247 full randomized clinical trial and NCT02377830 CYCLE Vanguard 46-patient internal pilot.).
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