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Abstract Rationale Studies have shown that reducing sedation of critically ill patients shortens time on the ventilator and in the intensive care unit (ICU). Little is known, however, of how such strategies affect long-term cognitive, psychological, and functional outcomes. Objectives To determine the long-term effects of a wake up and breathe protocol that interrupts and reduces sedative exposure in the ICU. Methods In this a priori planned substudy conducted at one tertiary care hospital during the Awakening and Breathing Controlled Trial, a multicenter randomized controlled trial, we assessed cognitive, psychological, and functional/quality-of-life outcomes 3 and 12 months postdischarge among 180 medical ICU patients randomized to paired daily spontaneous awakening trials with spontaneous breathing trials (SBTs) or to sedation per usual care plus daily SBTs. Measurements and Main Results Cognitive impairment was less common in the intervention group at 3-month follow-up (absolute risk reduction, 20.2%; 95% confidence interval, 1.5–36.1%; P = 0.03) but not at 12-month follow-up (absolute risk reduction, −1.9%; 95% CI, −21.3 to 27.1%; P = 0.89). Composite cognitive scores, alternatively, were similar in the two groups at 3-month and 12-month follow-up (P = 0.80 and 0.61, respectively), as were symptoms of depression (P = 0.59 and 0.82) and posttraumatic stress disorder (P = 0.59 and 0.97). Activities of daily living, functional status, and mental and physical quality of life were similar between groups throughout follow-up. Conclusions In this trial, management of mechanically ventilated medical ICU patients with a wake up and breathe protocol resulted in similar cognitive, psychological, and functional outcomes among patients tested 3 and 12 months post-ICU. The proven benefits of this protocol, including improved 1-year survival, were not offset by adverse long-term outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT00097630).

Approaches to removal of sedation and mechanical ventilation for critically ill patients vary widely. Our aim was to assess a protocol that paired spontaneous awakening trials (SATs)—ie, daily interruption of sedatives—with spontaneous breathing trials (SBTs). In four tertiary-care hospitals, we randomly assigned 336 mechanically ventilated patients in intensive care to management with a daily SAT followed by an SBT (intervention group; n=168) or with sedation per usual care plus a daily SBT (control group; n=168). The primary endpoint was time breathing without assistance. Data were analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00097630. One patient in the intervention group did not begin their assigned treatment protocol because of withdrawal of consent and thus was excluded from analyses and lost to follow-up. Seven patients in the control group discontinued their assigned protocol, and two of these patients were lost to follow-up. Patients in the intervention group spent more days breathing without assistance during the 28-day study period than did those in the control group (14·7 days vs 11·6 days; mean difference 3·1 days, 95% CI 0·7 to 5·6; p=0·02) and were discharged from intensive care (median time in intensive care 9·1 days vs 12·9 days; p=0·01) and the hospital earlier (median time in the hospital 14·9 days vs 19·2 days; p=0·04). More patients in the intervention group self-extubated than in the control group (16 patients vs six patients; 6·0% difference, 95% CI 0·6% to 11·8%; p=0·03), but the number of patients who required reintubation after self-extubation was similar (five patients vs three patients; 1·2% difference, 95% CI −5·2% to 2·5%; p=0·47), as were total reintubation rates (13·8% vs 12·5%; 1·3% difference, 95% CI −8·6% to 6·1%; p=0·73). At any instant during the year after enrolment, patients in the intervention group were less likely to die than were patients in the control group (HR 0·68, 95% CI 0·50 to 0·92; p=0·01). For every seven patients treated with the intervention, one life was saved (number needed to treat was 7·4, 95% CI 4·2 to 35·5). Our results suggest that a wake up and breathe protocol that pairs daily spontaneous awakening trials (ie, interruption of sedatives) with daily spontaneous breathing trials results in better outcomes for mechanically ventilated patients in intensive care than current standard approaches and should become routine practice.

Background One in eight children in the United Kingdom are estimated to have a mental health condition, and many do not receive support or treatment. The COVID-19 pandemic has negatively impacted mental health and disrupted the delivery of care. Prevalence of poor mental health is not evenly distributed across age groups, by sex or socioeconomic groups. Equity in access to mental health care is a policy priority but detailed socio-demographic trends are relatively under-researched. Methods We analysed records for all mental health prescriptions and referrals to specialist mental health outpatient care between the years of 2015 and 2021 for children aged 2 to 17 years in a single NHS Scotland health board region. We analysed trends in prescribing, referrals, and acceptance to out-patient treatment over time, and measured differences in treatment and service use rates by age, sex, and area deprivation. Results We identified 18,732 children with 178,657 mental health prescriptions and 21,874 referrals to specialist outpatient care. Prescriptions increased by 59% over the study period. Boys received double the prescriptions of girls and the rate of prescribing in the most deprived areas was double that in the least deprived. Mean age at first mental health prescription was almost 1 year younger in the most deprived areas than in the least. Referrals increased 9% overall. Initially, boys and girls both had an annual referral rate of 2.7 per 1000, but this fell 6% for boys and rose 25% for girls. Referral rate for the youngest decreased 67% but increased 21% for the oldest. The proportion of rejected referrals increased steeply since 2020 from 17 to 30%. The proportion of accepted referrals that were for girls rose to 62% and the mean age increased 1.5 years. Conclusions The large increase in mental health prescribing and changes in referrals to specialist outpatient care aligns with emerging evidence of increasing poor mental health, particularly since the start of the COVID-19 pandemic. The static size of the population accepted for specialist treatment amid greater demand, and the changing demographics of those accepted, indicate clinical prioritisation and unmet need. Persistent inequities in mental health prescribing and referrals require urgent action.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a number of chemotherapeutic agents. Drugs commonly implicated in the development of CIPN include platinum agents, taxanes, vinca alkaloids, bortezomib, and thalidomide analogues. As a drug response can vary between individuals, it is hypothesized that an individual’s specific genetic variants could impact the regulation of genes involved in drug pharmacokinetics, ion channel functioning, neurotoxicity, and DNA repair, which in turn affect CIPN development and severity. Variations of other molecular markers may also affect the incidence and severity of CIPN. Hence, the objective of this review was to summarize the known biological (molecular and genomic) predictors of CIPN and discuss the means to facilitate progress in this field.

For over a decade, Scotland has implemented and operationalized a system of Safe Havens, which provides secure analytics platforms for researchers to access linked, deidentified electronic health records (EHRs) while managing the risk of unauthorized reidentification. In this paper, a perspective is provided on the state-of-the-art Scottish Safe Haven network, including its evolution, to define the key activities required to scale the Scottish Safe Haven network’s capability to facilitate research and health care improvement initiatives. A set of processes related to EHR data and their delivery in Scotland have been discussed. An interview with each Safe Haven was conducted to understand their services in detail, as well as their commonalities. The results show how Safe Havens in Scotland have protected privacy while facilitating the reuse of the EHR data. This study provides a common definition of a Safe Haven and promotes a consistent understanding among the Scottish Safe Haven network and the clinical and academic research community. We conclude by identifying areas where efficiencies across the network can be made to meet the needs of population-level studies at scale.

Delirium is a common neurobehavioral syndrome that occurs across health care settings which is associated with adverse outcomes, including death. There are limited data on long-term cognitive outcomes following delirium. This report reviews the literature regarding relationships between delirium and cognitive impairment. Psych Info and Medline searches and investigation of secondary references for all English language articles on delirium and subsequent cognitive impairment were carried out. Nine papers met inclusion criteria and documented cognitive impairment in patients following delirium. Four papers reported greater cognitive impairment among patients with delirium than matched controls. Four papers reported higher incidence of dementia in patients with a history of delirium. One study found 1 of 3 survivors of critical illness with delirium developed cognitive impairment. The evidence suggests a relationship between delirium and cognitive impairment, although significant questions remain regarding the nature of this association. Additional research on delirium-related effects on long-term cognitive outcome is needed.

Purpose Our purpose was to create a content domain framework for delirium severity to inform item development for a new instrument to measure delirium severity. Methods We used an established, multi-stage instrument development process during which expert panelists discussed best approaches to measure delirium severity and identified related content domains. We conducted this work as part of the Better ASsessment of ILlness (BASIL) study, a prospective, observational study aimed at developing and testing measures of delirium severity. Our interdisciplinary expert panel consisted of twelve national delirium experts and four expert members of the core research group. Over a one-month period, experts participated in two rounds of review. Results Experts recommended that the construct of delirium severity should reflect both the phenomena and the impact of delirium to create an accurate, patient-centered instrument useful to interdisciplinary clinicians and family caregivers. Final content domains were Cognitive, Level of consciousness, Inattention, Psychiatric-Behavioral, Emotional dysregulation, Psychomotor features, and Functional. Themes debated by experts included reconciling clinical geriatrics and psychiatric content, mapping symptoms to one specific domain, and accurate capture of unclear clinical presentations. Conclusions We believe this work represents the first application of instrument development science to delirium. The identified content domains are inclusive of various, wide-ranging domains of delirium severity and are reflective of a consistent framework that relates delirium severity to potential clinical outcomes. Our content domain framework provides a foundation for development of delirium severity instruments that can help improve care and quality of life for patients with delirium.

Leading from the North aims to improve public dialogue around the future of Northern Australia to underpin robust and flexible planning and policy frameworks.

Purpose We present the findings of a structured systematic review of the literature assessing orofacial pain induced by malignant disease and/or its therapy (excluding mucositis). This evaluation of the literature published after the 1989 NIH Development Consensus conference on the oral complications of cancer therapies is an effort to assess the prevalence of pain, quality of life and economic impact, and management strategies for cancer therapy-induced orofacial pain. Methods A systematic medical literature search was conducted with assistance from a research librarian in MEDLINE/PubMed and EMBASE databases for articles published between January 1, 1990 and December 31, 2008. Each study was independently assessed by two reviewers with expertise in the field of oral oncology. Results Thirty-nine studies assessed pain in the head and neck region. The measure was commonly embedded in quality of life studies. Most of these studies described pain in head and neck cancer (HNC) patients, which therefore became the focus of the report. Pain is common in patients with HNC and is reported by approximately half of patients prior to cancer therapy, 81% during therapy, 70% at the end of therapy, and by 36% at 6 months after treatment. Pain is experienced beyond the 6-month period by approximately one third of patients and is typically more severe than pre-treatment cancer-induced pain. Conclusions This systematic review identified the presence of pain before cancer therapy, likely attributable to the cancer; an increase in pain during therapy and the common persistence of pain following cancer treatment. Continuing research should use validated tools to prospectively assess orofacial pain, its causes and pathophysiology, and its effect on quality of life and economic impact. Clinical trials of pain management in this setting are also warranted.

The ability to rate delirium severity is key to providing optimal care for older adults, and such ratings would allow clinicians to target patients with severe delirium and monitor response to treatment, recovery time, and prognosis; assess nursing burden and staffing needs; and, ultimately, provide more appropriate patient-centered care. Current delirium severity measures have been limited in their content, gradations, and measurement characteristics. To examine the internal consistency, reliability, and validity for clinical outcomes of the DEL-S delirium severity score, a measure of delirium severity that was developed using advanced psychometric approaches, analogous to those of the Patient-Reported Outcomes Measurement Information System initiative. This prospective cohort study was conducted at a large academic medical center in Boston, Massachusetts. Adults aged 70 years or older who were admitted or transferred to medical or surgical services as either emergency or elective admissions were enrolled between October 20, 2015, and March 15, 2017, and were monitored for 1 year. Data analysis was performed from June 2020 to August 2021. Delirium severity, measured by scores on the delirium severity score short-form (SF; 6 items, scored 0-13, with higher scores indicating more severe delirium) and long-form (LF; 17 items, scored 0-21), considered continuously and grouped into 5 categories. The primary outcomes were in-hospital outcomes, including length of stay and hospital costs, and posthospital (30, 90, and 365 days) outcomes, including death, health care costs, and rehospitalization. The 352 participants had a median (IQR) age of 79.7 (74.6-85.5) years, 204 (58.0%) were women, and they were highly educated (median [IQR] duration of education, 14 [7-20] years). Patients in the highest delirium severity score SF group (scores 6-9) had a longer length of stay (13.3 vs 6.9 days; P for trend < .001), greater in-hospital costs ($57 700 vs $34 200), greater cumulative health care costs ($168 700 vs $106 500; P for trend = .01), and increased mortality at 1 year (50% vs 17%; P for trend = .02) compared with patients in the lowest delirium severity score SF group (score 0). Similar trends and significant findings were demonstrated for the delirium severity score LF. These findings suggest that the delirium severity score provides an approach for measuring delirium severity that is associated with adverse clinical outcomes in a direct exposure-response association and that the delirium severity score may help advance patient-centered care for delirium.