Long-term cognitive impairment and delirium in intensive care: A prospective cohort study

Background: Whilst there is a growing body of research exploring the effect of delirium in intensive care unit (ICU) patients, the relationship between patient delirium and long-term cognitive impairment has not been investigated in settings where low rates of delirium have been reported. Objectives: To assess the association between the incidence of delirium, duration of mechanical ventilation and long term cognitive impairment in general ICU patients. Methods: Prospective cohort study conducted in a tertiary level ICU in Queensland, Australia. Adult medical and surgical ICU patients receiving ≥12. h mechanical ventilation were assessed for delirium on at least one day. Cognitive impairment was assessed at three and/or six-months using the: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS); Trail Making Test (TMT) Part A and B; and Mini-Mental State Examination (MMSE). Results: Of 148 enrollees, 91 (61%) completed assessment at three and/or six months. Incidence of delirium was 19%, with 41% cognitively impaired at three months and 24% remaining impaired at six months. Delirium was associated with impaired cognition at six-months: mean TMT Part A scores (information processing speed) were 7.86. s longer than those with no delirium (p = 0.03), and mean TMT Part B scores (executive functioning) 24.0. s longer (p = 0.04). Conclusions: ICU delirium was positively associated with impaired information processing speed and executive functioning at six-months post-discharge for this cohort. Testing for cognitive impairment with RBANS and TMT should be considered due to its greater sensitivity in comparison to the MMSE

A link between labor participation, mental health and class of medication for mental well-being

We examined the relationship between mental health and labor participation. Analysis was based on the Australian National Health Survey, providing a nationally representative sample using 14,788 observations. Accounting for endogeneity, analysis revealed that females were almost twice more responsive to changes in mental health on labor participation compared to males. Among Australians who did not take medication for mental wellbeing, poorer levels of mental health was associated with a reduction in the probability of labor participation. Among females with poorer mental health, taking any medication for mental well-being led to a decrease in the probability of labor participation. This relationship was not significant for males

Antipsychotic prescribing for vulnerable populations: a clinical audit at an acute Australian mental health unit at two-time points

Background: Antipsychotics are recognised as a critical intervention for schizophrenia and bipolar disorder. Guidelines globally endorse the routine practice of antipsychotic monotherapy, at the minimum effective dose. Even in treatmentresistant schizophrenia, clozapine use is endorsed before combining antipsychotics. This aim of this study was to review antipsychotic polytherapy alone, high-dose therapy alone, polytherapy and highdose prescribing patterns in adults discharged from an inpatient mental health unit at two time-points, and the alignment of this prescribing with clinical guideline recommendations. Additionally, associations with polytherapy and high-dose antipsychotic prescribing, including patient and clinical characteristics, were explored. Methods: A retrospective clinical audit of 400 adults (200 patients at two different time-points) discharged with at least one antipsychotic. Preliminary findings and education sessions were provided to physicians between Cohorts. Outcomes (polytherapy alone, high-dose therapy alone, polytherapy and high-dose therapy) were compared between study Cohorts using chi-squared and rank-sum tests. Associations between outcomes and covariates were assessed using multivariable logistic regression. Results: Most patients (62.5%) were discharged on a single antipsychotic within the recommended dose range. There was a clear preference for prescribing second generation antipsychotics, and in this respect, prescribing is aligned with current evidence-based guidelines. However, sub-optimal prescribing practices were identified for both Cohorts in relation to polytherapy and high-dose antipsychotic rates. Involuntary treatment, frequent hospitalisations and previous clozapine use significantly increased the risk of all three prescribing outcomes at discharge. Conclusions: In a significant minority, antipsychotic prescribing did not align with clinical guidelines despite increased training, indicating that the education program alone was ineffective at positively influencing antipsychotic prescribing practices. Further consideration should be given when prescribing antipsychotics for involuntary patients, people with frequent hospitalisations, and those who have previously trialled clozapine

Study protocol for The GOAL Trial: comprehensive geriatric assessment for frail older people with chronic kidney disease to increase attainment of patient-identified goals—a cluster randomised controlled trial

Background: An increasing number of older people are living with chronic kidney disease (CKD). Many have complex healthcare needs and are at risk of deteriorating health and functional status, which can adversely afect their quality of life. Comprehensive geriatric assessment (CGA) is an efective intervention to improve survival and independence of older people, but its clinical utility and cost-efectiveness in frail older people living with CKD is unknown. Methods: The GOAL Trial is a pragmatic, multi-centre, open-label, superiority, cluster randomised controlled trial developed by consumers, clinicians, and researchers. It has a two-arm design, CGA compared with standard care, with 1:1 allocation of a total of 16 clusters. Within each cluster, study participants≥65 years of age (or≥55 years if Aborigi‑ nal or Torres Strait Islander (First Nations Australians)) with CKD stage 3–5/5D who are frail, measured by a Frailty Index (FI) of>0.25, are recruited. Participants in intervention clusters receive a CGA by a geriatrician to identify medical, social, and functional needs, optimise medication prescribing, and arrange multidisciplinary referral if required. Those in standard care clusters receive usual care. The primary outcome is attainment of self-identifed goals assessed by standardised Goal Attainment Scaling (GAS) at 3 months. Secondary outcomes include GAS at 6 and 12 months, qual‑ ity of life (EQ-5D-5L), frailty (Frailty Index – Short Form), transfer to residential aged care facilities, cost-effectiveness, and safety (cause-specifc hospitalisations, mortality). A process evaluation will be conducted in parallel with the trial including whether the intervention was delivered as intended, any issue or local barriers to intervention delivery, and perceptions of the intervention by participants. The trial has 90% power to detect a clinically meaningful mean difference in GAS of 10 units. Discussion This trial addresses patient-prioritised outcomes. It will be conducted, disseminated and implemented by clinicians and researchers in partnership with consumers. If CGA is found to have clinical and cost-effectiveness for frail older people with CKD, the intervention framework could be embedded into routine clinical practice. The implementation of the trial’s findings will be supported by presentations at conferences and forums with clinicians and consumers at specifically convened workshops, to enable rapid adoption into practice and policy for both nephrology and geriatric disciplines. It has potential to materially advance patient-centred care and improve clinical and patient-reported outcomes (including quality of life) for frail older people living with CKD.B Logan ... MG Collins ... S Jesudason ... et al

The cost-effectiveness of a web-based multimodal therapy for unilateral cerebral palsy: The Mitii randomized controlled trial

Aim: To estimate the cost-effectiveness of the Mitii training system for improvements in upper limb function for children with unilateral cerebral palsy (CP). Mitii is a web-based programme delivered at home with set-up and monitoring by therapists. Method: A randomized controlled trial was conducted comparing the Mitii training programme to usual care. The Assessment of Motor and Process Skills (AMPS) and Canadian Occupational Performance Measure (COPM) were collected for each child at baseline and 20 weeks. Responders to training were characterized as those who met a minimally important difference on either the AMPS (0.3 logits) or COPM (2 points). Costs of the intervention were calculated by quantifying the equipment and staff cost. A cost per responder was calculated for each of the outcome measures. Results: A total of 102 participants (52 males, 50 females) were included in the analysis. There were significantly more responders in the training group on both the AMPS motor and process scales and the COPM performance and satisfaction scales. The cost per responder for the Mitii programme ranged from AU$3078 to AU$4191 depending on the scale used. Interpretation: The cost of delivering the Mitii training system is modest relative to the improvements in function

Reduced employment and financial hardship among middle-aged individuals with colorectal cancer

Financial hardship may affect up to 30% of cancer survivors, however, little research has addressed the effect of employment change on financial hardship. This study compared the self-reported financial hardship of middle-aged (45–64 years) colorectal cancer survivors (n = 187) at 6 and 12 months following diagnosis with that of a matched general population group (n = 355). Colorectal cancer survivors were recruited through the Queensland Cancer Registry, Australia; data from the Household Income and Labour Dynamics in Australia (HILDA) Survey were used for the general population group. Pearson chi-square tests were used to assess the differences in proportions between the two groups and McNemar tests to assess differences across time among the same group. Generalised linear modelling was performed to produce prevalence ratios. A higher proportion of workers with colorectal cancer reported financial strain (money shortage for living essentials) at 6 months (15%) but eased and was comparable to the comparison group at 12 months (7%). Middle-aged working cancer survivors who ceased or reduced work were more likely to report not being financially comfortable, compared with those who had continued work (adjusted prevalence ratio 1.66, 95%CI: 1.12, 2.44) at 12 months. Health professionals, employers and government services should address the impact of impaired employment on financial hardship among cancer survivors

Association between change in employment participation and quality of life in middle-aged colorectal cancer survivors compared with general population controls

Objective: This study aimed to examine the association between change in employment participation for a 12-month period and quality of life among individuals with colorectal cancer compared with general population controls. Methods: This was a prospective, registry-based study that enrolled middle-aged (45-64 years) residents of Queensland, Australia, who were in the paid workforce, and newly diagnosed with colorectal cancer. Participants completed structured telephone interviews at 6 and 12 months after diagnosis assessing quality of life and employment status (“retired/ceased work,” “increased work,” “decreased work,” and “maintained work”). Survivors were matched on demographic and occupation characteristics in a 1:2 ratio with individuals from the general population who had participated in both Wave 10 (2010) and 11 (2011) of the Household, Income and Labour Dynamics in Australia survey. Results: Almost half (66/148, 45%) of colorectal cancer survivors ceased or decreased work during the study period, compared with 27% in the control group (79/295, P =.001). Physical and mental well-being did not fluctuate over time in the general population. However, there were significant improvements in physical well-being, functional well-being, and overall quality of life during the study period for participants with colorectal cancer. At 12 months postdiagnosis, participants with colorectal cancer who maintained or increased work had significantly better functional well-being and overall quality of life compared with those who decreased work or retired. Conclusions: A diagnosis of colorectal cancer often impairs the ability of a person to maintain work. The impairments are predominantly physical and functional. Interventions to assist with occupational rehabilitation should be trialed.</p

Cancer put my life on hold

Background: Colorectal cancer affects a wide range of working-age people. Little is known about the consequent work limitations. Objective: The aim of this study was to understand the extent and changing nature of work-related limitations of middle-aged (45-64 years) people over the first 12 months of colorectal cancer. Methods: Surveys were administered to participants recruited via the Queensland Cancer Registry, at 6 and 12 months after diagnosis. Among those who returned to work, the Work Limitations Questionnaire measured 4 job performance domains (time management, physical, mental-interpersonal, and output demands) and an overall productivity score. Open-ended questions supplemented the Work Limitations Questionnaire, and responses were thematically analyzed. Results: Of 239 participants, 8% did not continue in the study, and 20% left employment by 12 months, leaving 171 participants eligible for this analysis. Open-ended responses for why participants stopped work included bowel problems and stoma, loss of strength, and medication adverse effects. At 12 months, 22% to 39% of participants reported work limitations, but there was no overall significant change in work limitations between 6 and 12 months. Qualitative data highlighted the key work-related issues were changes in work functioning, attitudes of employers and colleagues, financial pressures, and emotional responses. Conclusions: While a significant proportion left work because of treatment-related problems, and the majority of participants did not experience workplace limitations, some reported considerable work-related challenges.Implications for Practice: Discussions with health professionals about the possible impact of treatment adverse effects on employment, good communication with employers, and workplace flexibility may facilitate return to work for this population

Copper(II) interaction with unstructured prion domain outside the octarepeat region: speciation, stability and binding details of copper(II) complexes with PrP106-126 peptides”

Copper(II) complexes of the neurotoxic peptide fragments of human and chicken prion proteins were studied by potentiometric, UV-vis, CD, and EPR spectroscopic and ESI-MS methods. The peptides included the terminally blocked native and scrambled sequences of HuPrP106-126 (HuPrPAc106-126NH2 and ScrHuPrPAc106-126NH2) and also the nona- and tetrapeptide fragments of both the human and chicken prion proteins (HuPrPAc106- 114NH2, ChPrPAc119-127NH2, HuPrPAc109-112NH2, and ChPrPAc122-125NH2). The histidyl imidazole-N donor atoms were found to be the major copper(II) binding sites of all peptides; 3N and 4N complexes containing additional 2 and 3 deprotonated amide-N donors, respectively, are the major species in the physiological pH range. The complex formation processes for nona- and tetrapeptides are very similar, supporting the fact that successive deprotonation and metal ion coordination of amide functions go toward the N-termini in the form of joined six- and five-membered chelates. As a consequence, the peptide sequences investigated here, related to the neurotoxic region of the human PrP106-126 sequence, show a higher metal-binding affinity than the octarepeat fragments. In the case of the HuPrP peptide sequences, a weak pH-dependent binding of the Met109 residue was also detected in the 3N-coordinated complexes