Preoperative Anemia Prior to Gynecologic Surgery is Associated with Increased Healthcare Costs.

OBJECTIVE: To compare healthcare utilization costs between anemic and nonanemic patients undergoing elective hysterectomy and myomectomy for benign indications from the date of surgery to 30 days postoperatively. DESIGN: Retrospective population-based cohort study. SETTING: Single-payer publicly funded healthcare system in Ontario, Canada between 2013 and 2020. PARTICIPANTS: Adult women (≥18 years of age) who underwent elective hysterectomy or myomectomy (laparoscopic/laparotomy) for benign indications. INTERVENTIONS: Our exposure of interest was preoperative anemia, defined as the most recent hemoglobin value <12 g/dL on the complete blood count measured before the date of surgery. Our primary outcome was healthcare costs (total and disaggregated) from the perspective of the single-payer publicly funded healthcare system. RESULTS: Of the 59 270 patients in the cohort, 11 802 (19.9%) had preoperative anemia. After propensity matching, standardized differences in all baseline characteristics (N = 10 103 per group) were <0.10. In the matched cohort, the mean total healthcare cost per anemic patient was higher compared to cost per nonanemic patient ($6134.88 ± $2782.38 vs $6009.97 ± $2423.27, p < .001). Anemic patients, compared to nonanemic patients, had a higher mean difference in total healthcare cost of $124.91 per patient (95% CI $53.54-$196.29) translating to an increased cost attributable to anemia of 2.08% (95% CI 0.89%-3.28%, p < .001). In a subgroup analysis of patients undergoing hysterectomy (N = 9041), the cost was also significantly higher for anemic patients (mean difference per patient of $117.67, 95% CI $41.58-$193.75). For those undergoing myomectomy (N = 1062) the difference in cost was not statistically significant (mean difference $186.61, 95% CI -$17.42 to $390.65). CONCLUSION: Preoperative anemia was associated with significantly increased healthcare resource utilization and costs for patients undergoing elective gynecologic surgery. Although the cost difference per case was modest, when extrapolated to the population level, this difference could result in substantially significant cost to the healthcare system, attributable to preoperative anemia.

Pitfalls and Solutions in Mass Spectrometry-Based Identification of Protein Glycation.

Emerging evidence suggests that advanced glycation end-products (AGEs) such as Nε-(carboxymethyl)lysine (CML) and Nε-(carboxymethyl)lysine (CEL) may play important roles in certain human diseases. Reliable analytical methods are needed for their characterizations and measurements. Pitfalls have been reported for applications of LC-MS/MS to identify various types of post-translational modifications, but not yet for the case of AGEs. Here, we showed that in the absence of manual inspection, cysteine alkylation with 2-iodoacetamide (IAA) can result in false-positive/ambiguous identifications of CML >20%. They were attributed to offsite alkylation together with incorrect monoisotopic peak assignment (pitfall 1) or together with deamidation (pitfall 2). For pitfall 1, false-positive identifications can be alleviated using a peptide mass error tolerance ≤5 ppm during the database search. Pitfall 2 results in ambiguous modification assignments, which may be overcome by using other alkylation reagents. According to calculations of theoretical mass shifts, the use of other common alkylation reagents (iodoacetic acid, 2-chloroacetamide, and acrylamide) should face similar pitfalls. The use of acrylamide can result in false-positive identifications of CEL instead of CML. Subsequently, we showed that compared to IAA, the use of N-isopropylacrylamide (NIPAM) as an alkylation reagent achieved similar levels of proteome coverage, while reducing the offsite alkylation reactions at lysine by more than five times. Furthermore, false-positive/ambiguous identifications of CML due to the two types of pitfalls were absent when using NIPAM. NIPAM alkylation results in a unique mass shift that allows reliable identifications of CML and most likely other AGEs, such as CEL.

Utilization of Immunotherapy in Patients with Cancer Treated in Routine Care Settings: A Population-Based Study Using Health Administrative Data.

INTRODUCTION: The introduction of immunotherapy (IO) in the treatment of patients with cancer has significantly improved clinical outcomes. Population level information on actual IO utilization is limited. METHODS: We conducted a retrospective cohort study using provincial health administrative data from Ontario, Canada to: (1) assess the extent of IO use from 2011 (pre-IO funding) to 2019; and (2) identify factors associated with IO use in patients with advanced cancers for which IO is reimbursed including melanoma, bladder, lung, head and neck, and kidney tumors. The datasets were linked using a unique encoded identifier. A Fine and Gray regression model with death as a competing risk was used to identify factors associated with IO use. RESULTS: Among 59 510 patients assessed, 8771 (14.7%) received IO between 2011 and 2019. Use of IO increased annually from 2011 (3.3%) to 2019 (39.2%) and was highest in melanoma (52%) and lowest in head and neck cancer (6.6%). In adjusted analysis, factors associated with lower IO use included older age (hazard ratio (HR) 0.91 (95% CI, 0.89-0.93)), female sex (HR 0.85 (95% CI, 0.81-0.89)), lower-income quintile, hospital admission (HR 0.78 (95% CI, 0.75-0.82)), high Charlson score and de novo stage 4 cancer. IO use was heterogeneous across cancer centers and regions. CONCLUSION: IO utilization for advanced cancers rose substantially since initial approval albeit use is associated with patient characteristics and system-level factors even in a universal healthcare setting. To optimize IO utilization in routine practice, survival estimates and potential inequity in access should be further investigated and addressed.

Outcomes After Direct Discharge Home From Critical Care Units: A Population-Based Cohort Analysis.

OBJECTIVES: To compare health service use and clinical outcomes for patients with and without direct discharge to home (DDH) from ICUs in Ontario. DESIGN: Population-based, observational, cohort study using propensity scoring to match patients who were DDH to those not DDH and a preference-based instrumental variable (IV) analysis using ICU-level DDH rate as the IV. SETTING: ICUs in Ontario. PATIENTS: Patients discharged home from a hospitalization either directly or within 48 hours of care in an ICU between April 1, 2015, and March 31, 2017. INTERVENTION: DDH from ICU. MEASUREMENTS AND MAIN RESULTS: Among 76,737 patients in our cohort, 46,859 (61%) were DDH from the ICU. In the propensity matched cohort, the odds for our primary outcome of hospital readmission or emergency department (ED) visit within 30 days were not significantly different for patients DDH (odds ratio [OR], 1.00; 95% CI, 0.96-1.04), and there was no difference in mortality at 90 days for patients DDH (OR, 1.08; 95% CI, 0.97-1.21). The effect on hospital readmission or ED visits was similar in the subgroup of patients discharged from level 2 (OR, 0.98; 95% CI, 0.92-1.04) and level 3 ICUs (OR, 1.02; 95% CI, 0.96-1.09) and in the subgroups with cardiac conditions (OR, 1.03; 95% CI, 0.96-1.12) and noncardiac conditions (OR, 0.98; 95% CI, 0.94-1.03). Similar results were obtained in the IV analysis (coefficient for hospital readmission or ED visit within 30 d = -0.03 ± 0.03 ( se ); p = 0.3). CONCLUSIONS: There was no difference in outcomes for patients DDH compared with ward transfer prior to discharge when two approaches were used to minimize confounding within a large health systemwide observational cohort. We did not evaluate how patients are selected for DDH. Our results suggest that with careful patient selection, this practice might be feasible for routine implementation to ensure efficient and safe use of limited healthcare resources.

Trends in basal insulin prescribing in older adults with chronic kidney disease in Ontario, Canada: A population-based analysis from 2010 to 2020.

AIM: To examine trends in basal insulin prescribing in older adults with chronic kidney disease (CKD). MATERIALS AND METHODS: We conducted a population-based study of adults aged 66 years or older with treated diabetes from 1 January 2010 to 30 September 2020 in Ontario, Canada. We examined prevalent and incident prescriptions for human NPH, Levemir, glargine-100, Basaglar, glargine-300, and degludec insulin over 43 study intervals. We present trends in those with CKD, and in a subgroup, by estimated glomerular filtration rate (eGFR). To provide context for prescribing, we provide demographics, co-morbidities, and the healthcare utilization of included patients. RESULTS: In CKD, use of basal insulin was about 2-fold higher than in the general treated diabetes cohort. Prescriptions for NPH declined over time, while prescriptions for Levemir and glargine-100 increased until 2018 then decreased. Following drug formulary approval (September 2018), prescriptions for glargine-300 and degludec increased substantially. Incident prescriptions for basal insulin in CKD declined over time; however, in those with an eGFR of less than 30 ml/min/1.73m2 , rates remained stable. In recent years, rates of degludec and glargine-300 have rivalled glargine-100. CONCLUSIONS: In an era of new oral and injectable diabetes medications, the use of basal insulin has declined in older adults with CKD. However, in those with more advanced CKD, basal insulin, particularly newer analogues, remain a mainstay treatment.

Bariatric Center Designation and Outcomes Following Repeat Abdominal Surgery in Bariatric Patients.

INTRODUCTION: Repeat abdominal surgery in the bariatric surgery patient population may be challenging for non-bariatric-accredited institutions. The impact of regionalized bariatric care on clinical outcomes for bariatric surgery patients requiring repeat abdominal surgery is currently unknown. This study aims to investigate the association between bariatric center designation and clinical outcomes following hepatobiliary, hernia, and upper and lower gastrointestinal operations among patients with prior bariatric surgery. METHODS: This is a cohort study of a large sample of Ontario residents who underwent primary bariatric surgery between 2010 and 2017. A comprehensive list of eligible abdominal operations was captured using administrative data. The primary outcome was 30-d complications. Secondary outcomes included 30-d mortality, readmission, and length of stay. RESULTS: Among the 3301 study patients, 1305 (40%) received their first abdominal reoperation following bariatric surgery at a designated bariatric center. Nonbariatric center designation was not associated with significantly higher rates of 30-d complications (5.73% versus 5.72%), mortality (0.80% versus 0.77%), readmissions (1.11% versus 1.85%), or median postoperative length of stay (4 versus 4 d). After grouping the category of reoperations, upper gastrointestinal (odds ratio [OR] 0.66, confidence interval [CI] 0.39-1.11) and abdominal wall hernia surgery (OR 0.52, CI 0.27-0.99) showed a lower adjusted OR for complications among bariatric centers. CONCLUSIONS: Our study demonstrates that after adjustment for case-mix and patient characteristics, bariatric surgery patients undergoing repeat abdominal surgery at nonbariatric centers is not associated with higher proportion of complications or mortality. Complex hernia surgery may be considered the most appropriate for referral.

Survival and Health Care Use After Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVES: To compare long-term survival of Parkinson's disease (PD) patients with deep brain stimulation (DBS) to matched controls, and examine whether DBS was associated with differences in injurious falls, long-term care, and home care. METHODS: Using administrative health data (Ontario, Canada), we examined DBS outcomes within a cohort of individuals diagnosed with PD between 1997 and 2012. Patients receiving DBS were matched with non-DBS controls by age, sex, PD diagnosis date, time with PD, and a propensity score. Survival between groups was compared using the log-rank test and marginal Cox proportional hazards regression. Cumulative incidence function curves and marginal subdistribution hazard models were used to assess effects of DBS on falls, long-term care admission, and home care use, with death as a competing risk. RESULTS: There were 260 DBS recipients matched with 551 controls. Patients undergoing DBS did not experience a significant survival advantage compared to controls (log-rank test p = 0.50; HR: 0.89, 95% CI: 0.65-1.22). Among patients <65 years of age, DBS recipients had a significantly reduced risk of death (HR: 0.49, 95% CI: 0.28-0.84). Patients receiving DBS were more likely than controls to receive care for falls (HR: 1.56, 95% CI: 1.19-2.05) and home care (HR: 1.59, 95% CI: 1.32-1.90), while long-term care admission was similar between groups. CONCLUSIONS: Receiving DBS may increase survival for younger PD patients who undergo DBS. Future studies should examine whether survival benefits may be attributed to effects on PD or the absence of comorbidities that influence mortality.

Opioid Prescribing Practices for Women Undergoing Elective Gynecologic Surgery.

STUDY OBJECTIVE: To describe the opioid prescribing practices in opioid-naive women undergoing elective gynecologic surgery for benign indications and identify risk factors associated with increased perioperative opioid use. We also explored factors associated with new persistent opioid use in women with perioperative opioid use. DESIGN: Retrospective, population-based cohort study. SETTING: We used linked administrative data from a government-administered single-payer provincial healthcare system in Canada. This study was undertaken at ICES, a not-for-profit research institute in Ontario, Canada. PATIENTS: We followed opioid-naive adult women who underwent benign elective gynecologic surgery between 2013 and 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was perioperative opioid use defined as ≥1 opioid prescription from 30 days before to 14 days after surgery. New persistent opioid use after gynecologic surgery was defined as having filled 1 or more opioid prescriptions between 91 days and 180 days postoperatively. Multivariable log-linear regression analyses were employed to adjust for clinical and demographic data. Of the 132 506 patients included in our cohort, most (74.3%) underwent minor gynecologic procedures. Perioperative opioid use was documented in 27 763 (21.0%) patients, and there was a significant decreasing trend (p <.001) in the proportion of patients with perioperative opioid use from 21.8% in 2013 to 18.5% in 2018. Factors associated with increased perioperative opioid use included younger age; higher income quintile; urban dwellers; and diagnosis of infertility, endometriosis, or adnexal mass. Perioperative opioid use was an independent risk factor for persistent use (adjusted relative risk 1.40; 95% confidence interval, 1.13-1.72) and for every 65 patients prescribed opioids associated with gynecologic surgery, one developed new persistent opioid use. The highest risk factor for developing persistent use was filling a high-dose opioid prescription (adjusted relative risk5th quintileOME 2.33; 95% confidence interval, 1.83-2.96). CONCLUSION: One in 5 women who undergo a gynecologic procedure has a new exposure to opioids. For every 65 patients who fill an opioid prescription after their gynecologic surgery, one will experience prolonged opioid use.

First-Ever Ischemic Stroke and Incident Major Adverse Cardiovascular Events in 93 627 Older Women and Men.

Background and Purpose- Stroke risk is sex-specific, but little is known about sex differences of poststroke major adverse cardiovascular events (MACEs). Stroke-related brain damage causes autonomic dysfunction and inflammation, sometimes resulting in cardiac complications. Sex-specific cardiovascular susceptibility to stroke without the confounding effect of preexisting heart disease constitutes an unexplored field because previous studies focusing on sex differences in poststroke MACE have not excluded patients with known cardiovascular comorbidities. We therefore investigated sex-specific risks of incident MACE in a heart disease-free population-based cohort of patients with first-ever ischemic stroke and propensity-matched individuals without stroke. Methods- We included Ontario residents ≥66 years, without known cardiovascular comorbidities, with first-ever ischemic stroke between 2002 and 2012 and propensity-matched individuals without stroke. We investigated the 1-year risk of incident MACE (acute coronary syndrome, myocardial infarction, incident coronary artery disease, coronary revascularization procedures, incident heart failure, or cardiovascular death) separately for females and males. For estimating cause-specific adjusted hazard ratios, we adjusted Cox models for variables with weighted standardized differences >0.10 or those known to influence MACE risk. Results- We included 93 627 subjects without known cardiovascular comorbidities; 21 931 with first-ever ischemic stroke and 71 696 propensity-matched subjects without stroke. Groups were well-balanced on propensity-matching variables. There were 53 476 women (12 421 with and 41 055 without ischemic stroke) and 40 151 men (9510 with and 30 641 without ischemic stroke). First-ever ischemic stroke was associated with increased risk of incident MACE in both sexes. The risk was time-dependent, highest within 30 days (women: adjusted hazard ratio, 25.1 [95% CI, 19.3-32.6]; men: aHR, 23.4 [95% CI, 17.2-31.9]) and decreasing but remaining significant between 31 and 90 days (women: aHR, 4.8 [95% CI, 3.8-6.0]; men: aHR, 4.2 [95% CI, 3.3-5.4]), and 91 to 365 days (aHR, 2.1 [95% CI, 1.8-2.3]; men: aHR, 2.0 [95% CI, 1.7-2.3]). Conclusions- In this large population-based study, ischemic stroke was independently associated with increased risk of incident MACE in both sexes.

Factors associated with endocrine therapy adherence among post-menopausal women treated for early-stage breast cancer in Ontario, Canada.

PURPOSE: Adherence to adjuvant endocrine therapy among post-menopausal breast cancer patients is an important survivorship care issue. We explored factors associated with endocrine therapy adherence and survival in a large real-world population-based study. METHODS: We used health administrative databases to follow women (aged ≥ 66 years) who were diagnosed with breast cancer and started on adjuvant endocrine therapy from 2005 to 2010. Adherence was measured by medical possession ratio (MPR) and characterized as low (< 39% MPR), intermediate (40-79% MPR), or high (≥ 80% MPR) over a 5-year period. We investigated factors associated with adherence using a multinomial logistic regression model. Factors associated with all-cause mortality (5 years after starting endocrine therapy) were investigated using a multivariable Cox proportional hazards model. RESULTS: We identified 5692 eligible patients starting adjuvant endocrine therapy who had low, intermediate, and high adherence rates of 13% (n = 749), 13% (n = 733), and 74% (n = 4210), respectively. Lower rates of adherence were associated with increased age [low vs. high adherence: odds ratio (OR) 1.03, 95% CI 1.02-1.05 (per year); intermediate vs. high adherence: OR 1.02, 95% CI 1.01-1.04 (per year)]. High adherence was associated with previous use of adjuvant chemotherapy (low versus high adherence OR 0.42, 95% CI 0.30-0.59) and short-term follow-up with a medical oncologist within 4 months of starting endocrine therapy (low versus high adherence OR 0.83, 95% CI 0.69-0.99). Unadjusted analysis showed increased survival among patients with high endocrine therapy adherence. However, an independent association was no longer clearly detected after controlling for confounders. CONCLUSION: Interventions to improve adjuvant endocrine therapy adherence are warranted. Non-adherence may be a more significant issue among elderly patients. Short-term follow-up visit by a patient's medical oncologist after starting endocrine therapy may help to improve compliance.

Determinants of Direct Discharge Home From Critical Care Units: A Population-Based Cohort Analysis.

OBJECTIVE: To describe trends and patient and system factors associated with direct discharge from critical care to home in a large health system. DESIGN: Population-based cohort study of direct discharge to home rates annually over 10 years. We used a multivariable, multilevel random-effects regression model to analyze current factors associated with direct discharge home in a subcohort from the most recent 2 years. SETTING: One hundred seventy-four ICUs in 101 hospitals in Ontario. PATIENTS: All patients discharged from an ICU between April 1, 2007, and March 31, 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall, 237,200 patients (21.1%) were discharged directly home from an ICU. The rate of direct discharge to home increased from 18.6% in 2007 to 23.1% in 2017 (annual increase of 1.02; 95% CI, 1.02-1.03). There were marked variations in rates of direct discharge to home across all critical care units. For medical and surgical units, the median odds ratio was 1.76 (95% CI, 1.59-1.92). In these units, direct discharge to home was associated with younger age (odds ratio, 0.36; 95% CI, 0.34-0.39 for age 80-105 vs age 18-39), fewer comorbidities (odds ratio, 1.74; 95% CI, 1.63-1.85 for Charlson comorbidity index of 0 vs 2), diagnoses of overdose/poisoning (odds ratio, 1.35; 95% CI, 1.23-1.47) and diabetic complications (odds ratio, 1.35; 95% CI, 1.2-1.51), and admission after a same-day procedure (odds ratio, 2.82; 95% CI, 2.46-3.23 compared with emergency department). ICU occupancy was inversely associated with direct discharge to home with an odds ratio of 0.88 (95% CI, 0.87-0.88) for each 10% increase. CONCLUSIONS: High rates of direct discharge to home with evidence of significant practice variation combined with identifiable patient characteristics suggest that further evaluation of this increasingly common transition in care is warranted.

Disparities in Deep Brain Stimulation Use for Parkinson's Disease in Ontario, Canada.

OBJECTIVE: To examine whether sociodemographic characteristics and health care utilization are associated with receiving deep brain stimulation (DBS) surgery for Parkinson's disease (PD) in Ontario, Canada. METHODS: Using health administrative data, we identified a cohort of individuals aged 40 years or older diagnosed with incident PD between 1995 and 2009. A case-control study was used to examine whether select factors were associated with DBS for PD. Patients were classified as cases if they underwent DBS surgery at any point 1-year after cohort entry until December 31, 2016. Conditional logistic regression modeling was used to estimate the adjusted odds of DBS surgery for sociodemographic and health care utilization indicators. RESULTS: A total of 46,237 individuals with PD were identified, with 543 (1.2%) receiving DBS surgery. Individuals residing in northern Ontario were more likely than southern patients to receive DBS surgery [adjusted odds ratio (AOR) = 2.23, 95% confidence interval (CI) = 1.15-4.34]; however, regional variations were not observed after accounting for medication use among older adults (AOR = 1.04, 95% CI = 0.26-4.21). Patients living in neighborhoods with the highest concentration of visible minorities were less likely to receive DBS surgery compared to patients living in predominantly white neighborhoods (AOR = 0.27, 95% CI = 0.16-0.46). Regular neurologist care and use of multiple PD medications were positively associated with DBS surgery. CONCLUSIONS: Variations in use of DBS may reflect differences in access to care, specialist referral pathways, health-seeking behavior, or need for DBS. Future studies are needed to understand drivers of potential disparities in DBS use.

Risks of preoperative anemia in women undergoing elective hysterectomy and myomectomy.

BACKGROUND: Hysterectomy is one of the most common surgeries performed worldwide. Identification of modifiable risk factors for complications or readmissions could lead to targeted interventions to improve patient care and reduce health care costs. Preoperative anemia has been identified as a risk factor for adverse postoperative outcomes following noncardiac surgery. However, studies have not focused on young and healthy surgical populations, such as women undergoing gynecologic surgery for benign indications. OBJECTIVE: The purpose of this study was to evaluate whether preoperative anemia in women undergoing elective hysterectomy or myomectomy for benign indications was associated with increased 30 day postoperative morbidity and mortality. STUDY DESIGN: In this retrospective, population-based cohort study, we followed up adult women (≥18 years of age) who underwent elective hysterectomy or myomectomy (laparoscopic/laparotomy) between the years 2013 and 2015 for benign indications in Ontario, Canada. We used linked administrative data from a government-administered, single-payer provincial health care system using Canadian Classification of Health Interventions intervention codes, International Classification of Diseases, 10th revision, diagnostic codes, physician billing codes, and laboratory data from both community and hospital laboratories across the province. Our exposure of interest was preoperative anemia, defined as a hemoglobin value <12 g/dL on the complete blood count measured closest to the date of surgery. Our primary outcome was the composite of 30 day postoperative morbidity and mortality. Secondary outcomes were 5 individual components of the primary outcome: death, transfusion, surgical site infection, venothromboembolism, and return to the hospital within 30 days. To adjust for confounding, we generated a propensity score using a multiple logistic regression model in which the presence of anemia was regressed on all baseline characteristics. We matched anemic to nonanemic patients on the logit of the propensity score. Using an unadjusted log-binomial model estimated using generalized estimating equations to account for the matched pairs, we calculated the relative risk, 95% confidence intervals, and P values to evaluate the effect of anemia on outcomes. RESULTS: Of the 16,218 women in the cohort, 3664 (22.6%) had anemia. After propensity matching, standardized differences in all baseline characteristics (n = 3261 per group) were <0.10. In the matched cohort, the primary outcome (death, complications, or readmission) occurred in 41.2% of anemic patients and 36.2% of nonanemic patients (relative risk, 1.14, 95% confidence interval, 1.07-1.21, P < .0001; absolute risk reduction, 5.03%, 95% confidence interval, 2.70-7.36; (number needed to harm = 20). The risk of transfusion was significantly higher in anemic patients (relative risk, 3.25, 95% confidence interval, 2.67-3.95, P < .0001; absolute risk reduction, 8.34%, 95% confidence interval, 7.06-9.63; number needed to harm = 12). There was no difference in other secondary outcomes. In a subgroup analysis (women >55 years vs ≤55, n = 736), older women were at increased risk of the primary outcome (relative risk, 1.40, 95% confidence interval, 1.12-1.76, P = .004), transfusion (relative risk, 4.20, 95% confidence interval, 1.65-10.72, P = .003), surgical site infection (relative risk, 1.35, 95% confidence interval, 1.01-1.81, P = .04), and return to the hospital (relative risk, 2.36, 95% confidence interval, 1.54-3.62, P < .0001). CONCLUSION: Preoperative anemia in women undergoing elective hysterectomy/myomectomy was common and is an independent risk factor for 30 day postoperative adverse outcomes, especially in older women.

Gas-Phase Fragmentation Reactions of Protonated Cystine using High-Resolution Tandem Mass Spectrometry.

Cystine is an important biomolecule in living systems. Although collision-induced dissociation (CID)-based tandem mass spectrometry (MS/MS) is commonly applied for identification and quantification of cystine in both biomedical and nutritional studies, gas-phase fragmentation reactions of cystine in CID has remained unclear. This may lead to improper assay design, which may in turn result in inaccurate test results. In the present study, gas-phase fragmentation reactions of protonated cystine in CID were characterized using high-resolution MS/MS and pseudo MS³. Fragmentations started from cleavages of disulfide bond (S⁻S) and carbon⁻sulfur bond (C⁻S). When cleaving at the S⁻S, protonated cysteine was generated as one of the predominant fragmentation products. Minor fragmentations started from the loss of H2O + CO and the loss of NH3. Our results reveal that the m/z 74 fragment ion, which is commonly used as a product ion of the transition (precursor/product ion pair) in selected reaction monitoring (SRM) assay for quantifying cystine, comprises two isobaric fragments originating from different parts of cystine. This indicates the need for careful selection of a stable isotope-labeled cystine molecule as an internal standard for SRM assays. Here, we provide a clear picture of the fragmentation reactions of protonated cystine in CID. It can serve as a useful guidance for designing MS/MS-based assays for cystine testing.

Treatment and Mortality Following Cancer Diagnosis Among People With Non-affective Psychotic Disorders in Ontario, Canada: A Retrospective Cohort Study.

BACKGROUND AND HYPOTHESIS: People with psychotic disorders have a higher risk of mortality following cancer diagnosis, compared to people without psychosis. The extent to which this disparity is influenced by differences in cancer-related treatment is currently unknown. We hypothesized that, following a cancer diagnosis, people with psychotic disorders were less likely to receive treatment and were at higher risk of death than those without psychosis. STUDY DESIGN: We constructed a retrospective cohort of cases of non-affective psychotic disorder (NAPD) and a general population comparison group, using Ontario Health (OH) administrative data. We identified cases of all cancers diagnosed between 1995 and 2019 and obtained information on cancer-related treatment and mortality. Cox proportional hazards models were used to compare the probability of having a consultation with an oncologist and receiving cancer-related treatment, adjusting for tumor site and stage. We also compared the rate of all-cause and cancer-related mortality between the two groups, adjusting for tumor site. STUDY RESULTS: Our analytic sample included 24 944 people diagnosed with any cancer. People with NAPD were less likely to receive treatment than people without psychosis (HR = 0.87, 95% CI = 0.82, 0.91). In addition, people with NAPD had a greater risk of death from any cause (HR = 1.68, 95% CI = 1.60, 1.76), compared to people without NAPD. CONCLUSIONS: The lower likelihood of receiving cancer treatment reflects disparities in accessing cancer care for people with psychotic disorders, which may partially explain the higher mortality risk following cancer diagnosis. Future research should explore mediating factors in this relationship to identify targets for reducing health disparities.

Incidence of Total Knee Arthroplasty After Arthroscopic Surgery for Knee Osteoarthritis: A Secondary Analysis of a Randomized Clinical Trial.

Importance: It is unclear whether arthroscopic resection of degenerative knee tissues among patients with osteoarthritis (OA) of the knee delays or hastens total knee arthroplasty (TKA); opposite findings have been reported. Objective: To compare the long-term incidence of TKA in patients with OA of the knee after nonoperative management with or without additional arthroscopic surgery. Design, Setting, and Participants: In this ad hoc secondary analysis of a single-center, assessor-blinded randomized clinical trial performed from January 1, 1999, to August 31, 2007, 178 patients were followed up through March 31, 2019. Participants included adults diagnosed with OA of the knee referred for potential arthroscopic surgery in a tertiary care center specializing in orthopedics in London, Ontario, Canada. All participants from the original randomized clinical trial were included. Data were analyzed from June 1, 2021, to October 20, 2022. Exposures: Arthroscopic surgery (resection or debridement of degenerative tears of the menisci, fragments of articular cartilage, or chondral flaps and osteophytes that prevented full extension) plus nonoperative management (physical therapy plus medications as required) compared with nonoperative management only (control). Main Outcomes and Measures: Total knee arthroplasty was identified by linking the randomized trial data with prospectively collected Canadian health administrative datasets where participants were followed up for a maximum of 20 years. Multivariable Cox proportional hazards regression models were used to compare the incidence of TKA between intervention groups. Results: A total of 178 of 277 eligible patients (64.3%; 112 [62.9%] female; mean [SD] age, 59.0 [10.0] years) were included. The mean (SD) body mass index was 31.0 (6.5). With a median follow-up of 13.8 (IQR, 8.4-16.8) years, 31 of 92 patients (33.7%) in the arthroscopic surgery group vs 36 of 86 (41.9%) in the control group underwent TKA (adjusted hazard ratio [HR], 0.85 [95% CI, 0.52-1.40]). Results were similar when accounting for crossovers to arthroscopic surgery (13 of 86 [15.1%]) during follow-up (HR, 0.88 [95% CI, 0.53-1.44]). Within 5 years, the cumulative incidence was 10.2% vs 9.3% in the arthroscopic surgery group and control group, respectively (time-stratified HR for 0-5 years, 1.06 [95% CI, 0.41-2.75]); within 10 years, the cumulative incidence was 23.3% vs 21.4%, respectively (time-stratified HR for 5-10 years, 1.06 [95% CI, 0.45-2.51]). Sensitivity analyses yielded consistent results. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial of arthroscopic surgery for patients with OA of the knee, a statistically significant association with delaying or hastening TKA was not identified. Approximately 80% of patients did not undergo TKA within 10 years of nonoperative management with or without additional knee arthroscopic surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT00158431.

Gut-associated biomarkers L-FABP, I-FABP, and TFF3 and LIT score for diagnosis of surgical necrotizing enterocolitis in preterm infants.

OBJECTIVES: To evaluate the use of gut barrier proteins, liver-fatty acid binding protein (L-FABP), intestinal-fatty acid binding protein (I-FABP), and trefoil factor 3 (TFF3), as biomarkers for differentiating necrotizing enterocolitis (NEC) from septicemic/control infants and to identify the most severely affected surgical NEC from nonsurgical NEC infants. BACKGROUND: Clinical features and routine radiologic investigations have low diagnostic utilities in identifying surgical NEC patients. METHODS: The diagnostic utilities of individual biomarkers and the combination of biomarkers, the LIT score, were assessed among the NEC (n = 20), septicemia (n = 40), and control groups (n = 40) in a case-control study for the identification of proven NEC and surgical NEC infants. RESULTS: Plasma concentrations of all gut barrier biomarkers and the LIT score were significantly higher in the NEC than in the septicemia or control group (P < 0.01). Using median values of biomarkers and the LIT score in the NEC group as cutoff values for identifying NEC from septicemic/control cases, all had specificities of 95% or more and sensitivities of 50%. Significantly higher levels of biomarkers and the LIT score were found in infants with surgical NEC than in nonsurgical NEC cases (P ≤ 0.02). The median LIT score of 4.5 identified surgical NEC cases with sensitivity and specificity of 83% and 100%%, respectively. A high LIT score of 6 identified nonsurvivors of NEC with sensitivity and specificity of 78% and 91%, respectively. CONCLUSIONS: The LIT score can effectively differentiate surgical NEC from nonsurgical NEC infants and nonsurvivors of NEC from survivors at the onset of clinical presentation. Frontline neonatologists and surgeons may, therefore, target NEC infants who are most in need of close monitoring and those who may benefit from early surgical intervention.

A cross-sectional study of community-level physician retention and hospitalization in rural Ontario, Canada.

PURPOSE: Many rural communities experience poor family physician retention. We examined the association between community-level physician retention and hospitalization for all causes and ambulatory care-sensitive conditions (ACSCs) in 2017 among residents of rural communities in Ontario, Canada. METHODS: We conducted a population-based cross-sectional study by linking administrative data from the public health insurance program in Ontario. To create the physician retention measure for each rural community, we divided the number of family physicians who worked in the community in both 2016 and 2017 by the total number of unique family physicians in the community in either year. We grouped retention level by tertile and added a fourth category, "no physician" to include communities that did not have any residing physicians in either 2016 or 2017. Outcomes were all-cause hospitalization and ACSC hospitalization between April 1, 2017 and March 31, 2018. FINDINGS: Among 1,436,794 rural residents, there were 93,752 all-cause hospitalizations and 8,691 ACSC hospitalizations in 2017. After controlling for other predictors, compared to residents in low-retention communities, residents of medium- and high-retention communities were 0.888 (95% CI: 0.868-0.909) and 0.937 (95% CI: 0.915-0.960) times as likely to have all-cause hospitalization, and residents of high-retention communities were 0.918 (95% CI: 0.858-0.981) times as likely to have ACSC hospitalization in 2017. CONCLUSIONS: Community-level physician retention is significantly associated with all cause and ACSC hospitalization in rural communities in Ontario, and may serve as an alternate measure to assess the impact of disrupted continuity of care.

Evaluation of a modernized supported housing intervention for individuals who experience severe and persistent mental illness in Ontario, Canada.

WHAT IS KNOWN ON THE SUBJECT: Supported housing approaches that include case management and increased opportunities for independence and personal autonomy for people who are living with severe and persistent mental illness (SPMI) have been found to help reduce hospitalizations and use of the emergency department. What is not fully clear is if these types of supported housing arrangements also influence the use of primary health care and other specialist services. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE: This study uncovered that individuals experiencing SPMI who lived in supported housing used more primary health care and specialist physician services, in the year following transition to this housing arrangement. WHAT ARE THE IMPLICATIONS FOR PRACTICE: The findings of this study suggest that supported housing arrangements for people experiencing SPMI may help in improving the personalization of health services for individual residents, including increasing access to both primary health care and specialist services. This is important for nursing practice, as the findings of the study show that supported housing arrangements for people experiencing SPMI may assist in better supporting their complex health care needs. ABSTRACT: INTRODUCTION: Supported housing for people who are living with severe and persistent mental illness (SPMI) has been found to help reduce hospitalizations and use of the emergency department. What is not fully clear is if these types of supported housing arrangements also influence the use of primary health care and other specialist services. AIM/QUESTION: The aim of this study was to compare the use of health services use of individuals with SPMI, before and after transition to the new supported housing program. METHOD: Using health care administrative databases, a pre-post cohort study was conducted examining the health system use of residents who transitioned from custodial to supported housing arrangements between 2017 and 2019. RESULTS: Individuals with SPMI used more primary health care and specialist physician services after transition to the supported housing model. DISCUSSION: The results suggest that a supported housing model may be associated with increased usage of outpatient person-centred health services in people experiencing SPMI. IMPLICATIONS FOR PRACTICE: The findings of this study suggest that supported housing arrangements for people experiencing SPMI may help in improving the personalization of health services for individual. This is important for nursing practice, as the findings of the study show that supported housing arrangements may assist in better supporting complex health care needs of individuals.