Background:
Delirium is a common and distressing neurocognitive condition that frequently affects patients in palliative care settings and is often underdiagnosed.
Aim:
Expanding on a 2013 review, ...this systematic review examines the incidence and prevalence of delirium across all palliative care settings.
Design:
This systematic review and meta-analyses were prospectively registered with PROSPERO and included a risk of bias assessment.
Data sources:
Five electronic databases were examined for primary research studies published between 1980 and 2018. Studies on adult, non-intensive care and non-postoperative populations, either receiving or eligible to receive palliative care, underwent dual reviewer screening and data extraction. Studies using standardized delirium diagnostic criteria or valid assessment tools were included.
Results:
Following initial screening of 2596 records, and full-text screening of 153 papers, 42 studies were included. Patient populations diagnosed with predominantly cancer (n = 34) and mixed diagnoses (n = 8) were represented. Delirium point prevalence estimates were 4%–12% in the community, 9%–57% across hospital palliative care consultative services, and 6%–74% in inpatient palliative care units. The prevalence of delirium prior to death across all palliative care settings (n = 8) was 42%–88%. Pooled point prevalence on admission to inpatient palliative care units was 35% (confidence interval = 0.29–0.40, n = 14). Only one study had an overall low risk of bias. Varying delirium screening and diagnostic practices were used.
Conclusion:
Delirium is prevalent across all palliative care settings, with one-third of patients delirious at the time of admission to inpatient palliative care. Study heterogeneity limits meta-analyses and highlights the future need for rigorous studies.
IMPORTANCE: Although concussion treatment guidelines advocate rest in the immediate postinjury period until symptoms resolve, no clear evidence has determined that avoiding physical activity ...expedites recovery. OBJECTIVE: To investigate the association between participation in physical activity within 7 days postinjury and incidence of persistent postconcussive symptoms (PPCS). DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter cohort study (August 2013-June 2015) of 3063 children and adolescents aged 5.00-17.99 years with acute concussion from 9 Pediatric Emergency Research Canada network emergency departments (EDs). EXPOSURES: Early physical activity participation within 7 days postinjury. MAIN OUTCOMES AND MEASURES: Physical activity participation and postconcussive symptom severity were rated using standardized questionnaires in the ED and at days 7 and 28 postinjury. PPCS (≥3 new or worsening symptoms on the Post-Concussion Symptom Inventory) was assessed at 28 days postenrollment. Early physical activity and PPCS relationships were examined by unadjusted analysis, 1:1 propensity score matching, and inverse probability of treatment weighting (IPTW). Sensitivity analyses examined patients (≥3 symptoms) at day 7. RESULTS: Among 2413 participants who completed the primary outcome and exposure, (mean SD age, 11.77 3.35 years; 1205 39.3% females), PPCS at 28 days occurred in 733 (30.4%); 1677 (69.5%) participated in early physical activity including light aerobic exercise (n = 795 32.9%), sport-specific exercise (n = 214 8.9%), noncontact drills (n = 143 5.9%), full-contact practice (n = 106 4.4%), or full competition (n = 419 17.4%), whereas 736 (30.5%) had no physical activity. On unadjusted analysis, early physical activity participants had lower risk of PPCS than those with no physical activity (24.6% vs 43.5%; Absolute risk difference ARD, 18.9% 95% CI,14.7%-23.0%). Early physical activity was associated with lower PPCS risk on propensity score matching (n = 1108 28.7% for early physical activity vs 40.1% for no physical activity; ARD, 11.4% 95% CI, 5.8%-16.9%) and on inverse probability of treatment weighting analysis (n = 2099; relative risk RR, 0.74 95% CI, 0.65-0.84; ARD, 9.7% 95% CI, 5.7%-13.7%). Among only patients symptomatic at day 7 (n = 803) compared with those who reported no physical activity (n = 584; PPCS, 52.9%), PPCS rates were lower for participants of light aerobic activity (n = 494 46.4%; ARD, 6.5% 95% CI, 5.7%-12.5%), moderate activity (n = 176 38.6%; ARD, 14.3% 95% CI, 5.9%-22.2%), and full-contact activity (n = 133 36.1%; ARD, 16.8% 95% CI, 7.5%-25.5%). No significant group difference was observed on propensity-matched analysis of this subgroup (n = 776 47.2% vs 51.5%; ARD, 4.4% 95% CI, −2.6% to 11.3%). CONCLUSIONS AND RELEVANCE: Among participants aged 5 to 18 years with acute concussion, physical activity within 7 days of acute injury compared with no physical activity was associated with reduced risk of PPCS at 28 days. A well-designed randomized clinical trial is needed to determine the benefits of early physical activity following concussion.
Abstract
Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also ...present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007).
Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of "total Al"assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold.
The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3 that after complexation with O2*−, generate Al superoxides Al(O2*)(H2O5)+ 2. Semireduced AlO2* radicals deplete mitochondrial Fe and promote generation of H2O2, O2 * − and OH*. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates.
Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer's disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants.
The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances.
Obstructive sleep apnea syndrome is a major cause of morbidity in the Down syndrome population and is commonly treated with adenoidectomy and/or tonsillectomy (AT). However, these children are at ...increased risk for perioperative respiratory adverse events (PRAEs). The objective of this study was to examine risk factors for major PRAEs requiring intervention in children with Down syndrome undergoing AT and to describe their postoperative monitoring environment. This retrospective study included all children with Down syndrome aged 0–18 years who underwent a preoperative polysomnogram followed by AT at a tertiary pediatric institution. Descriptive statistics were used to summarize baseline demographic and clinical characteristics. A multivariable model for prediction of PRAEs was constructed. A priori, it was decided that minimum oxygen saturation, apnea–hypopnea index, and average oxygen saturation asleep would be included, along with medical comorbidities associated with PRAEs at
p
< 0.2 in univariable analyses. Fifty-eight children were included in this study; twelve had a PRAE. Cardiac disease was associated with PRAEs on univariable analysis (
p
= 0.03). In multivariable analysis, average oxygen saturation asleep was associated with PRAEs (OR 1.50; 95% confidence interval 1.00, 2.41;
p
= 0.05). For all of the remaining variables,
p
> 0.15. Fifty-six children were admitted for monitoring overnight; four were admitted to the intensive care unit and fifty-two were admitted to the ward.
Conclusions
: A multivariable model found evidence that lower average oxygen saturation while asleep was associated with PRAEs requiring intervention in children with Down syndrome. This study highlights the difficulty in predicting complications in this population.
What is known:
•
Obstructive sleep apnea syndrome is a major cause of morbidity in the Down syndrome population and is commonly treated with adenoidectomy and/or tonsillectomy.
•
However, children with Down syndrome are at increased risk for perioperative respiratory adverse events (PRAEs) following adenoidectomy and/or tonsillectomy.
What is new:
•
We found that a lower average oxygen saturation asleep is associated with increased odds of PRAEs, adjusting for age, total apnea–hypopnea index, cardiac comorbidity, and minimum oxygen saturation.
•
This study highlights the difficulty in predicting complications in this population.
Background
Spinal pain and major depression are prevalent conditions in adult populations and are particularly impactful in the military. However, the temporal relationship between these two ...conditions remains poorly understood.
Methods
Using data extracted from electronic medical records, we assessed the association between incident diagnoses of spinal pain and major depression in a cohort of 48,007 Canadian Armed Forces personnel followed from January 2017 to August 2018. We used multivariate Poisson regression to measure the association between the period prevalence of these two conditions. We used probabilistic bias modelling to correct our estimates for misclassification of spinal pain and major depression.
Results
After correcting for misclassification with probabilistic bias modelling, subjects newly diagnosed with spinal pain during the study period were 1.41 times (95% interval 1.25, 1.59) more likely also to be diagnosed with incident major depression, and personnel newly diagnosed with major depression were 1.28 times (95% interval 1.17, 1.39) more likely also to be diagnosed with spinal pain, compared to undiagnosed counterparts of the same age and sex. Without bias corrections, we would have overestimated the magnitude of the association between major depression and spinal pain by a factor of approximately 2.0.
Conclusion
Our results highlight a moderate and bi-directional association between two of the most prevalent disorders in military populations. Our results also highlight the importance of correcting for misclassification in electronic medical record data research.
IntroductionReference intervals and reference curves provide clinicians with a point of reference when evaluating patients’ laboratory test results. In practical applications, the 2.5th and 97.5th ...percentiles of healthy reference population are typically used as lower and upper reference limits. Guidelines outlining analytical and methodological steps involved in reference intervals and curves estimation are available and there have been large-scale world-wide initiatives to provide reference intervals and curves for children. However, there is a lack of synthesised evidence regarding the results of such initiatives in general, but specifically in iron-related biomarkers, ferritin (in serum and plasma) and haemoglobin. Objectives of this review are to identify studies that have produced reference intervals and curves for ferritin and haemoglobin in paediatric populations and to synthesise all available evidence. We also aim to quantify heterogeneity across reference intervals and curves and identify and elucidate sources of heterogeneity, including heterogeneity in the methods employed in their development.Methods and analysisUsing a comprehensive search strategy, we will identify eligible studies. Following electronic databases will be searched from inception: EMBASE, MEDLINE, SCOPUS and The Cochrane Library. We will also perform grey literature search to capture unpublished reference intervals and curves from healthy cohorts. Two researchers will independently screen retrieved citations against eligibility criteria in two stages, focusing first on titles and abstracts and then on full-text articles. Studies that provide reference intervals and curves for ferritin and haemoglobin for paediatric population will be eligible. Data extraction will include study characteristics, characteristics of reference population, methodological and analytical considerations and estimated reference intervals and curves. We will consider narrative synthesis and quantitative synthesis when appropriate.Ethics and disseminationEthical approval is not required as data from already published studies will be used. Results will be disseminated through peer-reviewed publications and conference presentations.PROSPERO registration numberCRD42023399802.
Background
Quinolones are popular antibiotics that are known for their potency, broad coverage, and reasonable safety. Concerns have been raised about a possible association between quinolones and ...retinal detachment (RD).
Methods
We conducted a nested case–control study using electronic health records (EHR) from the Health Facts® Database. The initial cohort included all patients who were admitted between 2000 and 2016, with no history of eye disease, and had a minimum medical history of one year. Eligible cases comprised inpatients who were first admitted with a primary diagnosis of RD between 2010 and 2015. Each eligible case was matched without replacement to five unique controls by sex, race, age, and period-at-risk. We used conditional logistic regression to calculate RD risk, adjusting for exposure to other medications, and major risk factors.
Results
We identified 772 cases and 3860 controls. Whereas our primary analysis of all subjects revealed no quinolone-associated RD risk, elevated but non-significant risks were noted in African Americans (ciprofloxacin and levofloxacin), those aged 56–70 years old (moxifloxacin), and women (ciprofloxacin).
Conclusion
Our study did not identify an elevated RD risk within 30 days following systemic administration of quinolone antibiotics. Suggestions of increased risk observed in some population subgroups warrant further investigation.
It is well established that high radon exposures increase the risk of lung cancer mortality. The effects of low occupational exposures and the factors that confound and modify this risk are not clear ...and are needed to inform current radiation protection of miners. The risk of lung cancer mortality at low radon exposures (< 100 working-level months) was assessed in the joint cohort analysis of Czech, French, and Canadian uranium miners, employed in 1953 or later. Statistical analysis was based on linear Poisson regression modeling with grouped cohort survival data. Two sensitivity analyses were used to assess potential confounding from tobacco smoking. A statistically significant linear relationship between radon exposure and lung cancer mortality was found. The excess relative risk per working-level month was 0.022 (95% confidence intervals: 0.013–0.034), based on 408 lung cancer deaths and 394,236 person-years of risk. Time since exposure was a statistically significant modifier; risk decreased with increasing time since exposure. A tendency for a decrease in risk with increasing attained age was observed, but this was not statistically significant. Exposure rate was not found to be a modifier of the excess relative risk. The potential confounding effect of tobacco smoking was estimated to be small and did not substantially change the radon–lung cancer mortality risk estimates. This joint cohort analysis provides strong evidence for an increased risk of lung cancer mortality from low occupational radon exposures. The results suggest that radiation protection measures continue to be important among current uranium miners.
Background:
Major depression is prevalent, impactful, and treatable in military populations, but not all depressed personnel seek professional care in a given year. Care-seeking patterns (including ...the use of primary vs. specialty care) and factors associated with the likelihood of mental health service utilization in depressed military personnel are poorly understood.
Methods:
Our sample included 520 Regular Force respondents to the 2013 Canadian Forces Mental Health Survey. All study participants had past-year major depression. Subjects reported whether they had spoken about their mental health with at least one health professional in the past 12 months. We used multivariate Poisson regression to explore factors associated with past-year mental health service use.
Results:
Three-quarters of Canadian military personnel with past-year depression had sought mental health care in the previous 12 months. Among care-seeking personnel, 70% had seen a psychologist or psychiatrist, while 5% had exclusively received care from a primary care physician. Belief in the effectiveness of mental health care was the factor most strongly associated with care seeking. Female gender, functional impairments, and psychiatric comorbidities were also associated with care seeking. Surprisingly, stigma perceptions had no independent association with care seeking.
Conclusions:
The proportion of depressed Canadian Armed Forces personnel who seek professional care and who access specialty mental health care is higher than in most other populations. However, an important minority of patients are not accessing health services. Efforts to further increase mental health service utilization in the Canadian military should continue to target beliefs about the effectiveness of mental health care.
Proximal humerus fractures are the third most common fracture in the elderly population and are expected to increase due to the aging population. Surgical fixation with locking plate technology has ...increased over the last decade despite a lack of proven superiority in the literature. Three previous randomized controlled trials have not shown a difference in patient-centered outcomes when comparing non-operative treatment with open reduction and internal fixation. Low patient enrollment and other methodological concerns however limit the generalizability of these conclusions and as a result, management of these fractures remains a controversy. By comparing the functional outcomes of locked plate surgical fixation versus non-operative treatment of displaced three and four-part proximal humerus fractures in the elderly population with a large scale, prospective, multi-centered randomized controlled trial, the optimal management strategy for this common injury may be determined.
We will conduct a prospective, single blind randomized controlled parallel arm trial to compare non-operative management of proximal humerus fractures with open reduction and internal fixation using locked plating technology. One-hundred and sixty patients > age 60 with acute 3- or 4- part proximal humerus fractures will be randomized to either open reduction and internal fixation with locked plating technology or non-operative management treatment arms. The primary outcome measure is the Constant Score at 24 months post-operative. Secondary outcome measures include the American Shoulder and Elbow Surgeon's Score (ASES), EuroQol EQ-5D-5 L Health Questionnaire Score, short form PROMIS upper extremity score and IPAQ for the elderly score. Further outcome measures include assessment of the initial classification, displacement and angulation and the quality of surgical reduction via a standard computed tomography (CT) scan; rates of non-union, malunion, arthrosis, osteopenia or other complications including infection, nerve injury, intra-articular screw penetration, reoperation rates and hospital re-admission rates.
The results of this trial will provide Level 1 evidence to guide decision-making in the treatment of proximal humerus fractures in the elderly population.
ClinicalTrials.gov NCT02362100 . Registered 5 Feb 2015.
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