Baseline Gastric Volume in Fasting Diabetic Patients Is Not Higher than That in Nondiabetic Patients: A Cross-sectional Noninferiority Study.

BACKGROUND: The physiology of diabetes mellitus can increase the risk of perioperative aspiration, but there is limited and contradictory evidence on the incidence of "full stomach" in fasting diabetic patients. The aim of this study is to assess the baseline gastric content (using gastric ultrasound) in diabetic and nondiabetic patients scheduled for elective surgery who have followed standard preoperative fasting instructions. METHODS: This was a prospective, noninferiority study of 180 patients (84 diabetic and 96 nondiabetic patients). Bedside ultrasound was used for qualitative and quantitative assessment of the gastric antrum in the supine and right lateral decubitus positions. Fasting gastric volume was estimated based on the cross-sectional area of the gastric antrum and a validated model. The hypothesis was that diabetic patients would not have a higher baseline fasting gastric volume compared to nondiabetic patients, with a noninferiority margin of 0.4 ml/kg. Secondary aims included the comparison of the incidence of full stomach (solid content or more than 1.5 mL/kg of clear fluid), estimation of the 95th percentile of the gastric volume distribution in both groups, and examination of the association between gastric volume, glycemic control, and diabetic comorbidities. RESULTS: The baseline gastric volume was not higher in diabetic patients (0.81 ± 0.61 ml/kg) compared to nondiabetic patients (0.87 ± 0.53 ml/kg) with a mean difference of -0.07 ml/kg (95% CI, -0.24 to 0.10 ml/kg). A total of 13 (15.5%) diabetic and 11 (11.5%) nondiabetic patients presented more than 1.5 ml/kg of gastric volume (95% CI for difference, -7.1 to 15.2%). There was little correlation between the gastric volume and either the time since diagnosis or HbA1C. CONCLUSIONS: The data suggest that the baseline gastric volume in diabetic patients who have followed standard fasting instructions is not higher than that in nondiabetic patients.

Lipidation of a bioactive cyclotide-based CXCR4 antagonist greatly improves its pharmacokinetic profile in vivo.

The CXCR4 chemokine is a key molecular regulator of many biological functions controlling leukocyte functions during inflammation and immunity, and during embryonic development. Overexpression of CXCR4 is also associated with many types of cancer where its activation promotes angiogenesis, tumor growth/survival, and metastasis. In addition, CXCR4 is involved in HIV replication, working as a co-receptor for viral entry, making CXCR4 a very attractive target for developing novel therapeutic agents. Here we report the pharmacokinetic profile in rats of a potent CXCR4 antagonist cyclotide, MCo-CVX-5c, previously developed in our group that displayed a remarkable in vivo resistance to biological degradation in serum. This bioactive cyclotide, however, was rapidly eliminated through renal clearance. Several lipidated versions of cyclotide MCo-CVX-5c showed a significant increase in the half-life when compared to the unlipidated form. The palmitoylated version of cyclotide MCo-CVX-5c displayed similar CXCR4 antagonistic activity as the unlipidated cyclotide, while the cyclotide modified with octadecanedioic (18-oxo-octadecanoic) acid exhibited a remarkable decrease in its ability to antagonize CXCR4. Similar results were also obtained when tested for its ability to inhibit growth in two cancer cell lines and HIV infection in cells. These results show that the half-life of cyclotides can be improved by lipidation although it can also affect their biological activity depending on the lipid employed.

Using the Cyclotide Scaffold for Targeting Biomolecular Interactions in Drug Development.

This review provides an overview of the properties of cyclotides and their potential for developing novel peptide-based therapeutics. The selective disruption of protein-protein interactions remains challenging, as the interacting surfaces are relatively large and flat. However, highly constrained polypeptide-based molecular frameworks with cell-permeability properties, such as the cyclotide scaffold, have shown great promise for targeting those biomolecular interactions. The use of molecular techniques, such as epitope grafting and molecular evolution employing the cyclotide scaffold, has shown to be highly effective for selecting bioactive cyclotides.

Effect of intravenous acetaminophen on postoperative outcomes in hip fracture patients: a systematic review and narrative synthesis.

PURPOSE: Hip fractures are debilitating in older adults because of their impact on quality of life. Opioids are associated with adverse effects in this population, so oral acetaminophen is commonly prescribed to minimize opioid use. Intravenous (iv) acetaminophen has been reported to have superior efficacy and bioavailability than oral acetaminophen. Nevertheless, its effect on postoperative outcomes in emergency hip fractures is unclear. This systematic review assessed the effect of iv acetaminophen on postoperative outcomes in older hip fracture patients. SOURCE: We searched multiple databases from inception to June 2021 for studies on adults > 50 yr of age undergoing emergency hip fracture surgery who received iv acetaminophen (or paracetamol) and that reported postoperative outcomes. Relevant titles, abstracts, and full texts were screened based on the eligibility criteria. The Newcastle-Ottawa scale was used to assess the quality of the selected papers. PRINCIPAL FINDINGS: Of 3,510 initial studies, four met the inclusion criteria. One was a prospective cohort study and three were retrospective cohort studies. All four studies used historical control groups. Three studies reported a significantly lower mean opioid dose with iv acetaminophen than with oral acetaminophen. Three studies also reported a significantly shorter hospital stay. One study each reported a significant decrease in the number of missed physical therapy sessions, the need for one-to-one supervision, and episodes of delirium. CONCLUSION: There is very limited low-level evidence that iv acetaminophen improves preoperative and postoperative analgesia and shortens hospital stay in older hip fracture patients. Nevertheless, our results should be interpreted with caution since there are no prospective randomized trials investigating whether iv acetaminophen improves postoperative outcomes in this patient population. STUDY REGISTRATION: PROSPERO (CRD42021198174); registered 15 August 2021.

RéSUMé: OBJECTIF: Les fractures de la hanche sont débilitantes chez les personnes âgées en raison de leur impact sur leur qualité de vie. Les opioïdes sont associés à des effets indésirables chez cette population, de sorte que l'acétaminophène par voie orale est couramment prescrit pour minimiser la consommation d'opioïdes. L'acétaminophène par voie intraveineuse (IV) a une efficacité et une biodisponibilité supérieures à celles de l'acétaminophène par voie orale. Néanmoins, son effet sur les devenirs postopératoires dans les fractures d'urgence de la hanche n'est pas clair. Cette revue systématique a évalué l'effet de l'acétaminophène IV sur les devenirs postopératoires chez les patients âgés avec une fracture de la hanche. SOURCES: Nous avons effectué des recherches dans plusieurs bases de données de leur création à juin 2021 pour en tirer les études portant sur des adultes > 50 ans bénéficiant d'une chirurgie d'urgence pour une fracture de la hanche et ayant reçu de l'acétaminophène IV (ou paracétamol), et qui rapportait les devenirs postopératoires. Les titres, résumés et textes intégraux pertinents ont été sélectionnés en fonction des critères d'admissibilité. L'échelle de Newcastle-Ottawa a été utilisée pour évaluer la qualité des articles sélectionnés. CONSTATATIONS PRINCIPALES: Sur les 3510 études initiales, quatre ont répondu aux critères d'inclusion. L'une était une étude de cohorte prospective et trois étaient des études de cohorte rétrospectives. Les quatre études ont utilisé des groupes témoins historiques. Trois études ont rapporté une dose moyenne d'opioïdes significativement plus faible avec l'acétaminophène IV qu'avec de l'acétaminophène par voie orale. Trois études ont également rapporté un séjour à l'hôpital significativement plus court. Une diminution significative du nombre de séances de physiothérapie manquées a été rapporté dans une étude, une autre a rapporté une diminution significative de la nécessité de supervision individuelle, et une troisième une réduction des épisodes d'état confusionnel aigu. CONCLUSION: : Il n'existe que très peu de données probantes qui sont de faible qualité et selon lesquelles l'acétaminophène IV améliore l'analgésie préopératoire et postopératoire et réduit la durée de séjour à l'hôpital chez les patients âgés atteints d'une fracture de hanche. Néanmoins, nos résultats doivent être interprétés avec prudence car il n'existe pas d'étude randomisée prospective évaluant si l'acétaminophène IV améliore les issues postopératoires dans cette population de patients. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021198174); enregistrée le 15 août 2021.

Determinants of Discharge Disposition From Acute Care for Survivors of Hypoxic-Ischemic Brain Injury: Results From a Large Population-Based Cohort Data Set.

OBJECTIVE: To identify determinants of discharge disposition from acute care among survivors of hypoxic-ischemic brain injury (HIBI), stratified by sex. DESIGN: Population-based retrospective cohort study using provincial data in Ontario, Canada. The determinants were grouped into predisposing, need, and enabling factors using the Anderson Behavioral Model. SETTING: Acute care. PARTICIPANTS: Survivors of HIBI aged ≥20 years at the time of hospitalization and discharged alive from acute care between April 1, 2002, and March 31, 2017. There were 7492 patients with HIBI, of whom 28% (N=2077) survived their acute care episode. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Discharge disposition from acute care, categorized as complex continuing care (CCC), long-term care (LTC), inpatient rehabilitation (IR), home with support, home without support, and transferred to another acute care. RESULTS: The discharge dispositions for the 2077 survivors were IR 23.4% (n=487), CCC 19.5% (n=404), LTC 6.2% (n=128), home without support 31.2% (n=647), home with support 15.1% (n=314), and other 4.6%. Multinomial multivariable logistic regression analysis using home without support as the reference category revealed that female patients were significantly more likely than male patients to be discharged to LTC/CCC. Those who were older, were frail, and had longer stay in acute care or special care unit (SCU) were more likely to be discharged to LTC/CCC. The only significant determinant for IR was longer stay in acute care. Survivors with cardiac-related injury were less likely to be discharged to LTC/CCC. Income was a significant factor for male patients but not for female patients in the sex-stratified analysis. The following variables were investigated but were not significant determinants in this study: need factors (comorbidity score, prior psychiatric disorders, health care utilization) and enabling factors (income quintile, rural area of residence). CONCLUSIONS: Predisposing (age, sex) and need factors (frailty, acute care days, SCU days, type of injury) were significant determinants of discharge disposition from acute care after HIBI. In spite of a system with universal coverage, sex differences were found, with more female patients being discharged to CCC/LTC rather than IR, controlling for age and other confounders. These findings should be considered in appropriate discharge planning from acute care for survivors of HIBI.

Interventions and cognitive functioning in adults with traumatic spinal cord injuries: a systematic review and meta-analysis.

AIM: This research synthesized scientific evidence on the impact of interventions for adults with traumatic spinal cord injury on cognition, to understand if current intervention approaches are appropriate in light of the risk of post-injury cognitive impairments. METHOD: Medline, Central, Embase, Scopus, PsycINFO and PubMed were searched for intervention in persons with SCI assessing cognition pre- and post-intervention. Study quality was completed using the National Institutes of Health quality assessment tools. Results were grouped by type of intervention. The meta-analysis involved calculation of pooled effect sizes for interventions utilizing the same cognitive measure. RESULTS: Eleven studies of moderate quality discussed drug therapy, transcutaneous tibial nerve stimulation, diet modification and dietary supplements, and inpatient rehabilitation. Some aspects of cognition were negatively affected by drugs while diet modification and supplement use, and transcutaneous tibial nerve stimulation showed no evidence of a difference in cognitive scores when compared with no intervention. Inpatient rehabilitation revealed a small but beneficial effect, when results of seven studies were pooled. CONCLUSION: Evidence on the effects of interventions on cognitive functioning in patients with traumatic spinal cord injury is sparse and inconclusive, so work in this area is timely. It is valuable to know not only which interventions are effective for improving cognition, but also how other commonly used interventions, intended to treat other injury sequela, can affect cognition. PROSPERO: CRD42018087238.Implications for rehabilitationHistorically, rehabilitation of patients with traumatic spinal cord injury has targeted physical impairments, with little attention to cognition; this research aimed to understand if current interventions are appropriate in light of the risk of patients' cognitive impairments. Evidence on the effects of drug therapy, diet and dietary supplements interventions on cognitive functioning in traumatic spinal cord injury is sparse and inconclusive.Combining multiple inpatient rehabilitation interventions shows a positive but heterogeneous effect on the cognitive functioning; interventions applied earlier show greater gains.A major challenge for clinicians is to select an outcome measure sensitive to change over time, and to relate the results to patients' change in cognitive abilities with intervention applicationResearch to understand the functional effect of spinal cord injury on the widely distributed networks of the central and autonomic nervous systems subserving cognition, is timely.

Predictors of suicide at time of diagnosis in schizophrenia spectrum disorder: A 20-year total population study in Ontario, Canada.

BACKGROUND: Suicide is a major cause of mortality for individuals with schizophrenia spectrum disorders (SSD). Understanding the risk factors for suicide at time of diagnosis can aid clinicians in identifying people at risk. METHODS: Records from linked administrative health databases in Ontario, Canada were used to identify individuals aged 16 through 45 years who received a first lifetime diagnosis of SSD (schizophrenia, schizoaffective disorder, psychotic disorder not otherwise specified (NOS)) using a validated algorithm between 01/01/1993 and 12/31/2010. The main outcome was death by suicide following cohort entry until 12/31/2012. OUTCOMES: 75,989 individuals with a first SSD diagnosis (60.1% male, 39.9% female) were followed for an average of 9.56 years. During this period, 1.71% of the total sample (72.1% male, 27.9% female) died by suicide, after an average of 4.32 years. Predictors of suicide death included male sex (HR 2.00, 95% CI 1.76-2.27), age at diagnosis between 26 and 35 (HR 1.27, 95% CI 1.10-1.45) or 36-45 (HR 1.34, 95% CI 1.16-1.54), relative to 16-25, and suicide attempt (HR 2.23, 95% CI 1.86-2.66), drug use disorder (HR 1.21, 95% CI 1.04-1.41), mood disorder diagnosis (HR 1.32, 95% CI 1.17-1.50), or mental health hospitalization (HR 1.30 95% CI 1.13-1.49) in the 2 years prior to SSD diagnosis. INTERPRETATION: Death by suicide occurs in 1 out of every 58 individuals and occurred early following first diagnosis of SSD. Psychiatric hospitalizations, mood disorder diagnoses, suicide attempts prior to SSD diagnosis, as well as a later age at first diagnosis, are all predictors of suicide and should be integrated into clinical assessment of suicide risk in this population.

Assault by strangulation: sex differences in patient profile and subsequent readmissions.

OBJECTIVES: Assault by strangulation has the potential for severe brain injury or death. The objectives of this study were to describe the profile of individuals who had strangulation-related emergency department (ED) or acute care visits, and to explore 1-year readmission outcomes among survivors. METHODS: A population-based retrospective cohort study was conducted using health administrative data in Ontario, Canada. Adults aged 15 years and older who were seen in the ED or acute care with assault by strangulation between fiscal years 2002/2003 and 2016/2017 were included in the study. Bivariate analyses were conducted to compare the patient profile and subsequent readmissions within 1 year of discharge, stratified by sex. RESULTS: A total of 586 patients were included in the study. The majority of these patients were seen in the ED (93%), predominantly female (70%), aged ≤ 39 years (68%), and of lower income quintiles of ≤ 3 (73%). Of the 579 patients who survived the initial admission, 52% had subsequent ED readmission and 21% had acute care readmission within 1 year. In sex-stratified analyses, a higher proportion of females were between 20 to 39 years (58.7% vs. 44.1%, p = 0.001), discharged home (88% vs. 81%, p < 0.001), and had ED readmission within 1 year of discharge (56% vs. 17%, p = 0.002). Males had comparatively higher 1-year acute care readmissions. CONCLUSION: The study shows high readmissions with sex differences among individuals with an assault by strangulation, suggesting sex-specific approach to health care practices to support the needs of this vulnerable population, thus reducing health system inefficiencies.

Predictors of in-hospital mortality following hypoxic-ischemic brain injury: a population-based study.

Objective: To identify predictors of in-hospital mortality following Hypoxic-Ischemic Brain Injury (HIBI) using the Anderson Behavioral Model.Design and Setting: Population based retrospective cohort study in Ontario, Canada with data collected between 1 April 2002 and 31 March 2017.Patients: Adult patients aged 20 years and older with HIBI-related acute care admission were identified in the health administrative data. Multivariable cox proportional hazard regression models were used to identify predisposing, need and enabling factors that predict in-hospital mortality.Results: Of the 7492 patients admitted to acute care with HIBI, the in-hospital mortality rate was 71%. The predisposing factors associated with mortality were female sex (HR, 1.16; 95% CI, 1.10-1.23) and older age (65-79 vs. 20-34: HR, 1.17; 95% CI, 1.02-1.35). The need factors associated with mortality were the presence of COPD (HR, 1.10; 95% CI, 1.02-1.17), psychiatric illness (HR, 1.13; 95% CI, 1.05-1.20) injury due to cardiac illness (HR, 1.19; 95% CI, 1.12-1.26) and longer emergency department length of stay. Having spending any time in an alternate level of care and the application of tracheotomy procedures were found to reduce mortality.Conclusions: The acute/critical care centers need to consider these findings to adopt prevention strategies targeting reduced in-hospital mortality.

Occupational and Physical Therapy Activities and Level of Effort in Patients With Traumatic Brain Injury: Association With Functional Outcomes.

BACKGROUND: Although some attention has been given to the association of functional outcomes with rehabilitation intensity, the evidence is still sparse in this field. OBJECTIVE: To investigate the effect of inpatient rehabilitation (IR) on discharge cognitive and motor function and the association of time spent in occupational and physical therapy and level of effort with cognitive and motor function in patients with traumatic brain injury (TBI). DESIGN: Secondary analysis of TBI-Practice Based Evidence dataset. SETTINGS: Inpatient rehabilitation. PARTICIPANTS: One hundred forty-nine patients with TBI who were consecutively admitted for IR between 2008 and 2011 in Ontario, Canada. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASUREMENTS: Admission and discharge Functional Independence Measure-Rasch Cognitive and Motor Scores. RESULTS: Patients showed significant improvement in cognitive and motor function from admission to discharge (P < .0001). After controlling for confounding factors, discharge FIM-Rasch cognitive and motor scores were not associated with either level of effort or time spent in physical therapy activities. Discharge motor, but not cognitive function, was associated with more time spent in the complex (ß = 0.20, confidence interval [CI] 0.005, 0.05) and less time spent in simple OT activities (ß = -0.13, CI -0.13, -0.01). CONCLUSION: This study provides valuable information for clinicians about the effectiveness of IR on the improvement of motor and cognitive outcomes and the importance of considering the amount of time spent in activities based on their level of complexity rather than the total time of therapy to improve motor outcomes in this population. LEVEL OF EVIDENCE: III.

Development of a novel short 12-meric papiliocin-derived peptide that is effective against Gram-negative sepsis.

The development of novel peptide antibiotics with potent activity against multidrug-resistant Gram-negative bacteria and anti-septic activity is urgently needed. In this study, we designed short, 12-meric antimicrobial peptides by substituting amino acids from the N-terminal 12 residues of the papiliocin (Pap12-1) peptide to alter cationicity and amphipathicity and improve antibacterial activity and bacterial membrane interactions. Pap12-6, with an amphipathic α-helical structure and Trp12 at the C-terminus, showed broad-spectrum antibacterial activity, especially against multidrug-resistant Gram-negative bacteria. Dye leakage, membrane depolarization, and electron microscopy data proved that Pap12-6 kills bacteria by permeabilizing the bacterial membrane. Additionally, Pap12-6 significantly reduced the secretion of NO, TNF-α, and IL-6 and secreted alkaline phosphatase reporter gene activity confirmed that Pap12-6 shows anti-inflammatory activity via a TLR4-mediated NF-κB signaling pathway. In a mouse sepsis model, Pap12-6 significantly improved survival, reduced bacterial growth in organs, and reduced LPS and inflammatory cytokine levels in the serum and organs. Pap12-6 showed minimal cytotoxicity towards mammalian cells and controlled liver and kidney damage, proving its high bacterial selectivity. Our results suggest that Pap12-6 is a promising peptide antibiotic for the therapeutic treatment of Gram-negative sepsis via dual bactericidal and immunomodulatory effects on the host.

Change in Function Over Inpatient Rehabilitation After Hypoxic Ischemic Brain Injury: A Population-Wide Cohort Study.

OBJECTIVE: To estimate change in motor, cognitive, and overall functional performance during inpatient rehabilitation (IR) and to identify potential determinants of these outcomes among patients with hypoxic-ischemic brain injury (HIBI). DESIGN: Population-based retrospective cohort study using Ontario's health administrative data. SETTING: Inpatient rehabilitation. PARTICIPANTS: Survivors of HIBI 20 years and older discharged from acute care between fiscal years 2002-2003 and 2010-2011 and admitted to IR within 1 year of acute care discharge (N=159). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Functional status as measured by FIM, total, and scores on motor and cognitive subscales. RESULTS: A higher proportion (77%) of HIBI patients in the study were male and 28% were older than 65 years. We observed material improvements in FIM total, motor, and cognitive scores from across the IR episode. Potential determinants of total FIM gain were living in rural location (ß, 10.4; 95% CI, 0.21-21), having shorter preceding acute care length of stay (15-30 vs >60 days ß, 10.4; 95% CI, 1.4-19.5), and failing to proceed directly to IR following acute care discharge (ß, 8.7; 95% CI, 1.8-15.5). Motor FIM gain had similar identified potential determinants. Identified potential determinants of cognitive FIM gain were shorter (ie, 31-60 vs >60 days) preceding acute care, longer IR and length of stay, and proceeding directly to IR. There were no sex differences in functional gain. CONCLUSIONS: Inpatient rehabilitation is beneficial to HIBI survivors. Timely access to these services may be crucial in achieving optimal outcomes for these patients.

Readmission following hypoxic ischemic brain injury: a population-based cohort study.

BACKGROUND: Readmission to acute care is common and is associated with indicators of suboptimal care and health system inefficiencies. The objective of this study was to identify independent determinants of readmission following survival of hypoxic ischemic brain injury. METHODS: We conducted a population-based retrospective cohort study using Ontario's administrative health data. Survivors of hypoxic ischemic brain injury aged 20 years or more discharged from acute care between fiscal years 2002/03 and 2010/11 were included. Multivariable negative binomial regression was used to identify independent determinants of both number of readmissions and cumulative duration of hospital stay(s) within 1 year after the index discharge. RESULTS: Of the 593 patients with hypoxic ischemic brain injury, 233 (39.3%) were readmitted within 1 year of the index acute care discharge. The number of readmissions was associated with age (35-49 yr v. 65-79 yr: rate ratio [RR] 0.57, 95% confidence interval [CI] 0.38-0.85; ≥ 80 yr v. 65-79 yr: RR 0.58, 95% CI 0.34-0.97) and higher comorbidity score (Johns Hopkins Aggregated Diagnosis Groups score > 30 v. < 10: RR 1.60, 95% CI 1.11-2.31). Cumulative readmission stay was associated with increased index acute care length of stay (31-90 d v. ≥ 90 d: RR 4.17, 95% CI 1.38-12.64), prior use of health care services (minimal v. very high: RR 0.15, 95% CI 0.05-0.49) and discharge disposition (home v. continuing/long-term care: RR 0.44, 95% CI 0.21-0.91). INTERPRETATION: The findings indicate a high readmission rate in the first year after the index acute care admission for survivors of hypoxic ischemic brain injury, reflecting care gaps and system inefficiencies. This suggests that bolstered discharge and home care planning and support are needed to address the specific needs of those with hypoxic ischemic brain injury.

Care of Youth in Their First Emergency Presentation for Psychotic Disorder: A Population-Based Retrospective Cohort Study.

OBJECTIVE: Emergency departments (EDs) are often the first point of care for youth with psychotic disorders; however, the care and aftercare they receive have not been well described. The aim of this study was to examine care and aftercare following first ED visit for psychotic disorder among youth. METHODS: We conducted a population-based retrospective cohort study of first ED presentations for psychotic disorder among youth 16 to 24 years old (N = 2,875) in Ontario, Canada. The youth were diagnosed with a psychotic disorder according to ICD-10 coding. We captured all first visits for psychotic disorder between April 2010 and March 2013. Our primary outcome was rate of outpatient mental health care within 30 days. We also examined factors associated with timely psychiatric aftercare, rates of outpatient mental health follow-up by provider type, ED revisit, and psychiatric admission within 30 days and 1 year. RESULTS: Forty percent of youth discharged to the community from their first ED presentation for psychotic disorder received no outpatient mental health care within 30 days. Factors associated with psychiatric aftercare included higher neighborhood income (income quintile 5 vs 1, hazard ratio [HR] = 1.48; 95% CI, 1.05-2.09; P = .026), rural residence (HR = 0.46; 95% CI, 0.31-0.70; P < .001), and mental health care in the 1 year before presentation (outpatient psychiatrist visit: HR = 1.89; 95% CI, 1.50-2.37; P < .001; psychiatric admission: HR = 0.71; 95% CI, 0.52-0.98; P = .038). CONCLUSIONS: Many youth do not receive timely follow-up after their first ED visit for psychotic disorder. There is an urgent need to improve service access for this vulnerable population.

Service utilization and suicide among people with schizophrenia spectrum disorders.

OBJECTIVE: To compare individuals with and without schizophrenia spectrum disorders (SSD) (schizophrenia, schizoaffective disorder, or psychotic disorder not otherwise specified) who die by suicide. METHOD: This is a retrospective case control study which compared all individuals who died by suicide in Ontario, Canada with (cases) and without (controls) SSD between January 1, 2008 and December 31, 2012. Cases (individuals with SSD) were compared to controls on demographics, clinical characteristics, and health service utilization proximal to suicide. A secondary analysis compared the characteristics of those with SSD and those with severe mental illness (defined as those without SSD who have had a psychiatric hospitalization within the five-years before suicide (excluding the 30 days prior to death)). RESULTS: Among 5650 suicides, 663 (11.7%) were by individuals with SSD. Compared to other suicides, SSD suicides were significantly more likely to be between the ages of 25-34. SSD suicide victims were significantly more likely to reside in the lowest income neighbourhoods and to reside in urban areas. SSD victims were also significantly more likely to have comorbid mood and personality disorders and all types of health service utilization, including outpatient mental health service contact in the 30 days prior to death, even when compared only with those who had a history of mental health hospitalization. CONCLUSIONS: Individuals with schizophrenia spectrum disorder account for over 1 in 10 suicide deaths, tend to be younger, poorer, urban, more clinically complex, and have higher rates of mental health service contact prior to death. The demographic and service utilization differences persist even when the SSD group is compared with a population with severe mental illness that is not SSD. Suicide prevention strategies for people with schizophrenia spectrum disorder should emphasize the importance of clinical suicide risk assessment during clinical encounters, particularly early in the course of illness.

Medium and long-term emergency department utilization after oesophagectomy: a population-based analysis.

OBJECTIVES: Oesophagectomy is a complex operation with the potential for prolonged recovery. The aim of this study was to evaluate healthcare resource utilization, specifically emergency department (ED) visits within 1 year of oesophagectomy, and to identify risk factors for ED visits and frequent ED use (FEDU). METHODS: A retrospective cohort study of consecutive oesophagectomies for cancer in all Ontario hospitals was conducted using linked health data (2000-2012) including the ability to identify ED visits at non-index hospitals. Ontario has a single-payer healthcare system with a population of 13.8-million people. Multivariable regression was used to identify independent factors associated with ED visits and FEDU (≥3 ED visits) within 1 year after oesophagectomy. RESULTS: There were 3344 oesophagectomies with in-hospital mortality of 5.8% (n = 193). Of those discharged, 16.4% (n = 549), 36.0% (n = 1203) and 55.8% (n = 1866) had ED visits within 30 days, 90 days and 1 year, respectively. Higher comorbidity [adjusted odds ratio (aOR) = 1.08, 95% confidence interval (CI): 1.05-1.11, P < 0.0001], rurality (aOR = 1.40, 95% CI: 1.10-1.78, P = 0.006) and receipt of chemotherapy and/or radiation therapy (aOR = 2.55, 95% CI: 2.12-3.08, P < 0.0001) were independent risk factors for ED visits within 1 year of oesophagectomy. Thoracoscopic-assisted surgery was independently associated with decreased ED visits (aOR = 0.67, 95% CI: 0.45-0.99, P = 0.049). Eight hundred and thirteen (24.3%) patients had FEDU. Higher comorbidity (aOR = 1.11, 95% CI: 1.08-1.14, P < 0.0001), rurality (aOR = 1.66, 95% CI: 1.31-2.10, P < 0.0001) and receipt of chemotherapy and/or radiation therapy (aOR = 2.38, 95% CI: 1.93-2.93, P < 0.0001) were independent risk factors for FEDU. One health region had more ED visits (P = 0.04) and more FEDU (P = 0.001) when compared with the other regions. There were higher ED visits and FEDU in the later years of the study period (both P < 0.0001). CONCLUSIONS: ED visits are common after oesophagectomy with almost 25% of patients having ≥3 visits and >50% having ≥1 visit within 1 year of oesophagectomy. We have identified demographic, surgical and regional risk factors for the potential targeted quality improvement.

Benzodiazepine prescription in Ontario residents aged 65 and over: a population-based study from 1998 to 2013.

BACKGROUND: Although commonly used in anxiety and insomnia, recent guidelines recommend caution when prescribing benzodiazepines in the elderly. Here we examined rates of benzodiazepine prescribing to older adults in Ontario, Canada from 1998 to 2013 and impact of legislation that made prescribing regulations more strict. METHOD: Annual benzodiazepine prescription rates for Ontario residents aged 65 and over were examined using the Ontario Drug Benefit database which captures all publicly funded prescriptions. Since most drugs, including benzodiazepines, are funded for residents aged ⩾65, data are essentially population-based. Weighted least squares regression methods were used to examine trends in prescribing rates (all benzodiazepines, anxiolytics, hypnotics, short- and long-acting drugs and individual drugs) from 1998 to 2013 for all Ontario residents aged ⩾65 and by sex and 5-year age bands. Impact on monthly prescribing rates of legislative changes (November 2011) which aimed to promote appropriate prescribing and dispensing practices for controlled substances, including requiring prescribers to record specified information, was assessed by constructing an interrupted time-series model. RESULTS: Benzodiazepines were prescribed to 23.2% of the 1,412,638 Ontario residents aged ⩾65 in 1998, declining to 14.9% of 2,057,899 residents aged ⩾65 in 2013 (p < 0.001 for trend). Rates were significantly greater throughout in older age bands (p < 0.001) and 1.54-1.62 times greater in females than males (p < 0.001). Lorazepam was the most prescribed benzodiazepine throughout, but rates declined from 11.4% in 1998 to 8.5% in 2013. Diazepam rates fell from 2.3% to 0.7%. However, clonazepam prescription rates increased until 2011, 1.7-fold overall. After the November 2011 legal changes, downward shifts were observed in total benzodiazepine prescription rates and for each drug individually. The step function, conditional on covariates, suggested benzodiazepine rates after November 2011 were 2.89 per 1000 (p < 0.001) below rates observed previously, representing a relative reduction of 4.8% compared to the year before the intervention. CONCLUSION: Benzodiazepine prescribing rates declined markedly in this population from 1998 to 2013. Targeted legislation may have reduced rates, but the effect, although statistically significant, was small.

Cost Analysis of a High Support Housing Initiative for Persons with Severe Mental Illness and Long-Term Psychiatric Hospitalization.

OBJECTIVE: The objective of this article was to conduct a cost analysis comparing the costs of a supportive housing intervention to inpatient care for clients with severe mental illness who were designated alternative-level care while inpatient at the Centre for Addiction and Mental Health in Toronto. The intervention, called the High Support Housing Initiative, was implemented in 2013 through a collaboration between 15 agencies in the Toronto area. METHOD: The perspective of this cost analysis was that of the Ontario Ministry of Health and Long-Term Care. We compared the cost of inpatient mental health care to high-support housing. Cost data were derived from a variety of sources, including health administrative data, expenditures reported by housing providers, and document analysis. RESULTS: The High Support Housing Initiative was cost saving relative to inpatient care. The average cost savings per diem were between $140 and $160. This amounts to an annual cost savings of approximately $51,000 to $58,000. When tested through sensitivity analysis, the intervention remained cost saving in most scenarios; however, the result was highly sensitive to health system costs for clients of the High Support Housing Initiative program. CONCLUSIONS: This study suggests the High Support Housing Initiative is potentially cost saving relative to inpatient hospitalization at the Centre for Addiction and Mental Health.

Patterns of methadone maintenance treatment provision in Ontario: Policy success or pendulum excess?

OBJECTIVE: To describe recent trends and patterns in methadone maintenance treatment (MMT) practice regionally and over time in the province of Ontario. DESIGN: Population-based descriptive study using health administrative data between September 1, 2011, and December 31, 2014. SETTING: Ontario. PARTICIPANTS: All active MMT-prescribing physicians and patients receiving MMT in the study period. MAIN OUTCOME MEASURES: Characteristics of MMT-prescribing physicians, including age, sex, specialty type, practice region, and practice volume; characteristics of patients receiving MMT, including age, sex, neighbourhood income, and region of residence. RESULTS: Between September 1, 2011, and December 31, 2014, the number of MMT-prescribing physicians and patients who received MMT increased by 26% and 42%, respectively. In 2014, there was a total of 312 MMT-prescribing physicians and 49 703 patients receiving MMT. In 2014 and on a per capita basis, patients receiving MMT were more prevalent in rural regions; and within rural regions, there were disproportionately large numbers of young female MMT patients residing in low-income neighbourhoods. CONCLUSION: The number of physicians prescribing MMT and patients receiving MMT has increased substantially between 2011 and 2014, with the largest per capita distribution occurring in rural regions and involving young adults. While availability of and access to MMT has improved considerably from before 2000 to levels of high use, these developments are likely influenced by recent trends in the proliferation of prescription opioid misuse across general populations.

Quality of Diabetes Care for Individuals with Comorbid Chronic Psychotic Illness: A Sex-Based Analysis.

BACKGROUND: Diabetes is common among individuals with chronic psychotic illness, yet they receive lower quality of diabetes care than those without psychosis. Men usually receive higher quality diabetes care than women, but whether this holds true in chronic psychotic illness populations is unknown. We aimed to determine whether quality of diabetes care differs between men and women with chronic psychotic illness. METHODS: This population-based cohort study used Ontario health administrative data to compare women and men with comorbid chronic psychotic illness and diabetes mellitus (2011-2013). The primary outcome was adherence to diabetes monitoring guidelines, defined as ≥1 retinal exam, ≥4 hemoglobin A1c (HbA1c) tests, and ≥1 dyslipidemia test during a 2-year period. Logistic regression models compared women to men to generate adjusted odds ratios (aOR) and confidence intervals (95% CI), adjusting for potential confounding variables. RESULTS: Women with chronic psychotic illness (n = 13,972) were slightly more likely to receive guideline-adherent diabetes monitoring than men (n = 12,287) (25.2% vs. 23.0%; aOR 1.20, 95% CI 1.10-1.30), including a greater likelihood of receiving ≥1 retinal exam (aOR 1.13, 95% CI 1.08-1.19) and ≥4 HbA1c tests (aOR 1.06, 95% CI 1.01-1.12). There was no difference in receipt of ≥1 dyslipidemia test (aOR 1.04, 95% CI 0.99-1.11). CONCLUSIONS: Quality of diabetes monitoring is similarly poor in women and men with chronic psychotic illness, with women receiving only marginally more optimal monitoring than men. This differs from patterns in the general population, and could have implications when designing and implementing interventions to improve diabetes care in women and men with chronic psychotic illness.