Functional disability and disease activity are affected by social determinants of health in patients with rheumatoid arthritis.

BACKGROUND: The relationship between social determinants of health (SDH) and disease outcomes in rheumatoid arthritis (RA) is not well documented. METHODS: Data were extracted from the Ontario Best Practices Research Initiative (OBRI) registry for patients between January 2008 and April 2022. Adjusted mixed models analysis was used to investigate the effect of baseline SDH on disease activity (Clinical Disease Activity Index (CDAI)) and functional disability (Health Assessment Questionnaire-Disability Index (HAQ-DI)) 12 months after enrollment. The analyses were completed on multiple imputed data. RESULTS: There were 2651 patients with a mean age of 58.1 years (SD 12.9). The majority (77.8%) were female. Greater improvements in physical function were seen in patients who were full-time employed (difference = - 0.20; 95% CI - 0.28, - 0.11), part-time employed (difference = - 0.10; 95% CI - 0.19, - 0.02), or retired (difference = - 0.17; 95% CI - 0.25, - 0.08), compared to unemployed, those with highest income ($75,000 or more) (difference = - 0.23; 95% CI - 0.37, - 0.09). Caucasian was also associated with a positive impact on functional ability (difference = - 0.09; 95% CI - 0.17, - 0.02). In contrast, smokers had smaller improvements in physical function (difference = 0.07; 95% CI 0.002, 0.14). Interestingly, women had greater improvement in CDAI (difference = - 2.40; 95% CI - 3.29, - 1.51), while they reported less improving in their physical function (difference = 0.33; 95% CI 0.27-0.39). Achieving CDAI low disease activity/remission state was also more common in females. CONCLUSIONS: Our findings suggest that disease activity and functional disability are affected by different SDH factors. The effects of SDH should be better understood and addressed by rheumatologists to provide equitable healthcare for all patients with RA. Key points • This study explored a comprehensive panel of social determinants of health and their relationship to clinical outcomes. • Previously unreported factors such as employment status and income were found to influence clinical outcomes. • Our findings can help physicians to identify high-risk patients who may benefit from additional attention to their social background.

Intensity of survivin expression linked to features of aggressive relapsed/refractory diffuse large B-cell lymphoma.

SPiReL is a phase II clinical trial evaluating combination immunotherapy, pembrolizumab and cyclophosphamide, with maveropepimut-S, in survivin-expressing relapsed/refractory (R/R) Diffuse Large B Cell Lymphoma (DLBCL). We describe baseline tumor survivin expression and associations with clinico-pathological variables in 25 participants. The median number of survivin-expressing cells was 99%, and the intensity of survivin expression within tumors was heterogeneous by semi-quantitative immunohistochemistry assessment. Tumors with higher numbers of cells expressing 2+/3+ survivin were associated with characteristics of poor outcome, (Lactate dehydrogenase and cell-of-origin). Greater total baseline tumor area was associated with lower proportions of 1+ cells and greater proportions of 2+/3+ cells. High intensity survivin expression is associated with aggressive clinical features supporting a pathobiological role in R/R DLBCL. Future prognostic models incorporating survivin as a clinical biomarker require assessment of intensity, overall expression and should include potential threshold effects of survivin in DLBCL pathobiology.

Nocturnal Cardiac Arrhythmias in Heart Failure With Obstructive and Central Sleep Apnea.

BACKGROUND: Both OSA and central sleep apnea (CSA) may contribute to nocturnal cardiac arrhythmias (NCAs). Data are scarce regarding the prevalence of clinically important nocturnal atrial and ventricular arrythmias in patients with heart failure with reduced ejection fraction (HFrEF) and OSA or CSA. RESEARCH QUESTION: In a cohort of patients with HFrEF, how does the prevalence of NCA compare among those with OSA, CSA, and those with no to mild sleep apnea? Is the severity of OSA or CSA associated with atrial and ventricular NCAs? STUDY DESIGN AND METHODS: This cross-sectional analysis is an ancillary study of the Effect of Adaptive Servo Ventilation on Survival and Hospital Admissions in Heart Failure (ADVENT-HF) trial. We compared the prevalence of NCAs (excessive supraventricular ectopic activity [ESVEA], defined as premature atrial complexes ≥30/h or supraventricular tachycardia ≥ 20 beats); atrial fibrillation/flutter [AF]; and > 10 premature ventricular complexes [PVC/h]) on ECGs from polysomnograms of patients with HFrEF between those with OSA (apnea-hypopnea index [AHI ≥ 15 events/h]), those with CSA (AHI ≥ 15 events/h), and those with no to mild sleep apnea (AHI < 15 events/h [control]). RESULTS: The prevalence of ESVEA was higher in patients with OSA (n = 430) and CSA (n = 150) compared with control participants (n = 76): 0%, 9%, and 12%, respectively. The prevalence of AF in the control, OSA, and CSA groups was 9%, 17%, and 27%; the prevalence of > 10 PVC/h was 45%, 59%, and 63%. In multivariable regression analyses, premature atrial complexes/h was associated with OSA severity (obstructive AHI: 22.4% increase per 10 events/h [95% CI, 5.2-42.3; P = .009), although neither obstructive nor central AHI was associated with AF or > 10 PVC/h. INTERPRETATION: In patients with HFrEF, the prevalences of nocturnal ESVEA, AF, and PVC > 10/h were higher in those with OSA or CSA than in those without OSA or CSA, and OSA severity was related to the burden of nocturnal atrial ectopy. Severity of OSA or CSA was not significantly related to AF or > 10 PVC/h. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT01128816; URL: www. CLINICALTRIALS: gov.

Lateralized Subthalamic Stimulation for Axial Dysfunction in Parkinson's Disease: Exploratory Outcomes and Open-Label Extension.

BACKGROUND: A randomized trial suggested that reducing left-sided subthalamic stimulation amplitude could improve axial dysfunction. OBJECTIVES: To explore open-label tolerability and associations between trial outcomes and asymmetry data. METHODS: We collected adverse events in trial participants treated with open-label lateralized settings for ≥3 months. We explored associations between trial outcomes, location of stimulation and motor asymmetry. RESULTS: 14/17 participants tolerated unilateral amplitude reduction (left-sided = 10, right-sided = 4). Two hundred eighty-four left-sided and 1113 right-sided stimulated voxels were associated with faster gait velocity, 81 left-sided and 22 right-sided stimulated voxels were associated with slower gait velocity. Amplitude reduction contralateral to shorter step length was associated with 2.4-point reduction in axial MDS-UPDRS. Reduction contralateral to longer step length was associated with 10-point increase in MDS-UPDRS. CONCLUSIONS: Left-sided amplitude reduction is potentially more tolerable than right-sided amplitude reduction. Right-sided more than left-sided stimulation could be associated with faster gait velocity. Shortened step length might reflect contralateral overstimulation.

Evaluating associations between patient-to-nurse ratios and mortality, process of care events and vital sign documentation on paediatric wards: a secondary analysis of data from the EPOCH cluster-randomised trial.

OBJECTIVE: To describe the associations between patient-to-nurse staffing ratios and rates of mortality, process of care events and vital sign documentation. DESIGN: Secondary analysis of data from the evaluating processes of care and outcomes of children in hospital (EPOCH) cluster-randomised trial. SETTING: 22 hospitals caring for children in Canada, Europe and New Zealand. PARTICIPANTS: Eligible hospitalised patients were aged>37 weeks and <18 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was all-cause hospital mortality. Secondary outcomes included five events reflecting the process of care, collected for all EPOCH patients; the frequency of documentation for each of eight vital signs on a random sample of patients; four measures describing nursing perceptions of care. RESULTS: A total of 217 714 patient admissions accounting for 849 798 patient days over the course of the study were analysed. The overall mortality rate was 1.65/1000 patient discharges. The median (IQR) number of patients cared for by an individual nurse was 3.0 (2.8-3.6). Univariate Bayesian models estimating the rate ratio (RR) for the patient-to-nurse ratio and the probability that the RR was less than one found that a higher patient-to-nurse ratio was associated with fewer clinical deterioration events (RR=0.88, 95% credible interval (CrI) 0.77-1.03; P (RR<1)=95%) and late intensive care unit admissions (RR=0.76, 95% CrI 0.53-1.06; P (RR<1)=95%). In adjusted models, a higher patient-to-nurse ratio was associated with lower hospital mortality (OR=0.77, 95% CrI=0.57-1.00; P (OR<1)=98%). Nurses from hospitals with a higher patient-to-nurse ratio had lower ratings for their ability to influence care and reduced documentation of most individual vital signs and of the complete set of vital signs. CONCLUSIONS: The data from this study challenge the assumption that lower patient-to-nurse ratios will improve the safety of paediatric care in contexts where ratios are low. The mechanism of these effects warrants further evaluation including factors, such as nursing skill mix, experience, education, work environment and physician staffing ratios. TRIAL REGISTRATION NUMBER: EPOCH clinical trial registered on clinical trial.gov NCT01260831; post-results.

Inferior vena cava ultrasound to predict hypotension after general anesthesia induction: a systematic review and meta-analysis of observational studies.

PURPOSE: Hypotension after induction of general anesthesia is common and is associated with significant adverse events. Identification of patients at high risk can inform the use of preoperative mitigation strategies. We conducted a systematic review and meta-analysis to assess the diagnostic accuracy of the inferior vena cava collapsibility index (IVC-CI) and maximal diameter (dIVCmax) in predicting postinduction hypotension and to identify their predictive performance across different threshold ranges. METHODS: We searched MEDLINE, PubMed®, and Embase from inception to March 2023 for prospective observational studies exploring the performance of IVC-CI and dIVCmax in predicting postinduction hypotension in adults presenting for elective surgery under general anesthesia. We excluded studies reporting on IVC parameters predicting postinduction hypotension in the obstetric patient population or exclusively in patients with obesity. Trials screening and data extraction were conducted independently. We performed meta-analyses to identify the performance of IVC parameters in predicting postinduction hypotension, followed by subgroup analyses that sought the IVC-CI range with the highest hierarchical summary receiver-operating characteristic area under the curve (HSROC-AUC). We used a bivariate random effects model to calculate summary estimates. We evaluated study quality using Newcastle-Ottawa scores and certainty of evidence using the GRADE framework. RESULTS: We included 14 studies involving 1,166 patients. Pooled sensitivity and specificity of the IVC-CI to predict postinduction hypotension was 0.68 (95% confidence interval [CI], 0.55 to 0.79; coverage probability, 0.91) and 0.78 (95% CI, 0.69 to 0.85; coverage probability, 0.9), respectively, with an HSROC-AUC of 0.80 (95% CI, 0.68 to 0.85, high quality of evidence). An IVC-CI threshold range of 40-45% had an HSROC-AUC of 0.86 (95% CI, 0.69 to 0.93, high quality of evidence). CONCLUSIONS: Preoperative IVC-CI is a strong predictor of postinduction hypotension. We recommend that future studies use an IVC-CI threshold of 40-45% (low certainty of evidence). Future studies are needed to establish whether ultrasound-guided preoperative optimization improves outcomes in high-risk patients. STUDY REGISTRATION: PROSPERO ( CRD42022316140 ); first submitted 10 March 2022.

RéSUMé: OBJECTIF: L'hypotension après l'induction de l'anesthésie générale est fréquente et est associée à des effets indésirables importants. L'identification des patient•es à haut risque peut éclairer l'utilisation de stratégies préopératoires d'atténuation. Nous avons réalisé une revue systématique et une méta-analyse pour évaluer la précision diagnostique de l'indice de collapsibilité de la veine cave inférieure (IC-VCI) et du diamètre maximal (dVCImax) pour prédire l'hypotension post-induction et identifier leurs performances prédictives dans différentes plages de seuils. MéTHODE: Nous avons fait des recherches dans les bases de données MEDLINE, PubMed® et Embase de leur création jusqu'en mars 2023 pour en extraire les études observationnelles prospectives explorant les performances de l'IC-VCI et du dVCImax pour la prédiction de l'hypotension post-induction chez des adultes se présentant pour une chirurgie non urgente sous anesthésie générale. Nous avons exclu les études rapportant des paramètres de VCI prédisant l'hypotension post-induction dans la population obstétricale ou exclusivement chez des personnes obèses. Le tri des études et l'extraction des données ont été menés indépendamment. Nous avons réalisé des méta-analyses pour identifier la performance des paramètres de VCI dans la prédiction de l'hypotension post-induction, suivies d'analyses de sous-groupes qui ont recherché la plage d'IC-VCI avec le plus haut niveau de hiérarchie de l'aire sous la courbe de la courbe ROC (HSROC-AUC). Nous avons utilisé un modèle bivarié à effets aléatoires pour calculer des estimations sommaires. Nous avons évalué la qualité des études à l'aide des scores de Newcastle-Ottawa et la certitude des données probantes à l'aide de l'outil GRADE. RéSULTATS: Quatorze études portant sur 1166 patient·es ont été incluses. La sensibilité et la spécificité combinées de l'IC-VCI pour prédire l'hypotension post-induction étaient de 0,68 (intervalle de confiance [IC] à 95 %, 0,55 à 0,79; probabilité de couverture, 0,91) et 0,78 (IC 95 %, 0,69 à 0,85; probabilité de couverture, 0,9), respectivement, avec une HSROC-AUC de 0,80 (IC 95 %, 0,68 à 0,85, données probantes de haute qualité). Une plage de seuils d'IC-VCI de 40 à 45 % avait une HSROC-AUC de 0,86 (IC 95 %, 0,69 à 0,93, haute qualité des données probantes). CONCLUSION: L'IC-VCI préopératoire est un bon prédicteur de l'hypotension post-induction. Nous recommandons que les études futures utilisent un seuil d'IC-VCI de 40 à 45 % (faible certitude des données probantes). De futures études sont nécessaires pour déterminer si l'optimisation préopératoire échoguidée améliore les devenirs chez la patientèle à risque élevé. ENREGISTREMENT DE L'éTUDE: PROSPERO ( CRD42022316140 ); première soumission le 10 mars 2022.

Impact of dexamethasone on transplant-related mortality in pediatric patients: a multi-site, propensity score-weighted, retrospective assessment.

Dexamethasone use during hematopoietic cell transplant (HCT) conditioning varies between pediatric centers. This study aimed to estimate the difference in 1-year treatment-related mortality (TRM) between patients who did or did not receive dexamethasone during HCT conditioning. Secondary objectives were to estimate the difference between dexamethasone-exposed and dexamethasone-unexposed groups in 1-year event-free survival (EFS), time to neutrophil engraftment, acute graft-versus-host disease (aGVHD), and invasive fungal disease (IFD) at day + 100. This was a seven-site, international, retrospective cohort study. Patients < 18 years old undergoing their first allogeneic or autologous myeloablative HCT for hematologic malignancy or aplastic anemia between January 1, 2012, and July 31, 2017, were included. To control for potential confounders, propensity score weighting was used to calculate the standardized mean difference for all endpoints. Among 242 patients, 140 received dexamethasone during HCT conditioning and 102 did not. TRM was unaffected by dexamethasone exposure (1.7%; 95% CI - 7.4, 10.2%). Between-group differences in secondary outcomes were small. However, dexamethasone exposure significantly increased possible, probable, and proven IFD incidence (9.0%, 95% CI 0.8, 17.3%). TRM is not increased in pediatric patients who receive dexamethasone during HCT conditioning. Clinicians should consider potential IFD risk when selecting chemotherapy-induced vomiting prophylaxis for pediatric HCT patients.

Derivation and Initial Validation of the Utility Function for the Hearing Utility Measure (HUM).

OBJECTIVE: The Hearing Utility Measure (HUM) is a replacement hearing attribute for the Health Utilities Index, Mark 3 (HUI-3) designed to improve the responsiveness of utility estimates to changes in hearing-related quality of life. The final development step is to derive the instrument's utility scoring function. METHODS: Residents of Ontario, Canada, aged ≥18 years participated in standard gamble and visual analogue scale exercises. Valuations for levels (response options) within each domain, and for each domain relative to the other domains were elicited and used to generate a hearing utility function. The function outputs hearing utility ranging from 0 = 'unable to hear at all' to 1 = 'perfect hearing' for each of the 25,920 hearing states classifiable by the HUM. Performance was assessed relative to the criterion standard: directly elicited standard gamble utility. Distributions of HUM-derived hearing utility were compared with legacy HUI-3 derived estimates. RESULTS: A total of 126 respondents participated (mean age 39.2, range 18-85 years, 53% female [67/126]). The utility function performed well in the estimation of directly elicited utilities (mean difference 0.03, RMSE 0.06). Using the legacy HUI-3, estimated hearing utility was 1.0 for 118/126 respondents (93.6%) compared with just 66/126 (52.4%) using the HUM. CONCLUSION: The new hearing attribute is capable of measuring variations in hearing utility not captured by the legacy HUI-3, especially near the ceiling of hearing function. These findings justify its application and further work to study its measurement properties in hearing loss populations. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:4754-4762, 2024.

What Is the Potential Value of a Randomized Trial of Different Thresholds to Initiate Invasive Ventilation? A Health Economic Analysis.

OBJECTIVES: To estimate the expected value of undertaking a future randomized controlled trial of thresholds used to initiate invasive ventilation compared with usual care in hypoxemic respiratory failure. PERSPECTIVE: Publicly funded healthcare payer. SETTING: Critical care units capable of providing invasive ventilation and unconstrained by resource limitations during usual (nonpandemic) practice. METHODS: We performed a model-based cost-utility estimation with individual-level simulation and value-of-information analysis focused on adults, admitted to critical care, receiving noninvasive oxygen. In the primary scenario, we compared hypothetical threshold A to usual care, where threshold A resulted in increased use of invasive ventilation and improved survival compared with usual care. In the secondary scenario, we compared hypothetical threshold B to usual care, where threshold B resulted in decreased use of invasive ventilation and similar survival compared with usual care. We assumed a willingness-to-pay of 100,000 Canadian dollars (CADs) per quality-adjusted life year. RESULTS: In the primary scenario, threshold A was cost-effective compared with usual care due to improved hospital survival (78.1% vs. 75.1%), despite more use of invasive ventilation (62% vs. 30%) and higher lifetime costs (86,900 vs. 75,500 CAD). In the secondary scenario, threshold B was cost-effective compared with usual care due to similar survival (74.5% vs. 74.6%) with less use of invasive ventilation (20.2% vs. 27.6%) and lower lifetime costs (71,700 vs. 74,700 CAD). Value-of-information analysis showed that the expected value to Canadian society over 10 years of a 400-person randomized trial comparing a threshold for invasive ventilation to usual care in hypoxemic respiratory failure was 1.35 billion CAD or more in both scenarios. CONCLUSIONS: It would be highly valuable to society to identify thresholds that, in comparison to usual care, either increase survival or reduce invasive ventilation without reducing survival.

Hydroxyurea dose optimisation for children with sickle cell anaemia in sub-Saharan Africa (REACH): extended follow-up of a multicentre, open-label, phase 1/2 trial.

BACKGROUND: Realizing Effectiveness Across Continents with Hydroxyurea (REACH) is an open-label non-randomised trial of hydroxyurea (hydroxycarbamide) in children with sickle cell anaemia in sub-Saharan Africa. The short-term results of REACH on safety, feasibility, and effectiveness of hydroxyurea were published previously. In this paper we report results from extended hydroxyurea treatment in the REACH cohort up to 8 years. METHODS: In this open-label, non-randomised, phase 1/2 trial, participants were recruited from four clinical sites in Kilifi, Kenya; Mbale, Uganda; Luanda, Angola; and Kinshasa, Democratic Republic of Congo. Eligible children were 1-10 years old with documented haemoglobin SS or haemoglobin Sß zero thalassaemia, weighing at least 10 kg. Participants received fixed-dose hydroxyurea of 17.5 (±2.5) mg/kg per day for 6 months (fixed-dose phase), followed by 6 months of dose escalation (2·5-5·0 mg/kg increments every 8 weeks) as tolerated, up to 20-35 mg/kg per day (maximum tolerated dose; MTD), defined as mild myelosuppression. After the MTD was reached, hydroxyurea dosing was optimised for each participant on the basis of changes in bodyweight and laboratory values over time (MTD with optimisation phase). After completion of the first 12 months, children with an acceptable toxicity profile and favourable responses were given the opportunity to continue hydroxyurea until the age of 18 years. The safety and feasibility results after 3 years has been reported previously. Here, haematological responses, clinical events, and toxicity rates were compared across the dosing phases (fixed-dose hydroxyurea vs MTD with optimisation phase) as protocol-specified outcomes. REACH is registered on ClinicalTrials.gov (NCT01966731) and is ongoing. FINDINGS: We enrolled 635 children between July 4, 2014, and Nov 11, 2016. 606 children were given hydroxyurea and 522 (86%; 266 [51%] boys and 256 [49%] girls) received treatment for a median of 93 months (IQR 84-97) with 4340 patient-years of treatment. The current (Oct 5, 2023) mean dose is 28·2 (SD 5·2) mg/kg per day with an increased mean haemoglobin concentration (7·3 [SD 1·1] g/dL at baseline to 8·5 [1·5] g/dL) and mean fetal haemoglobin level (10·9% [SD 6·8] to 23·3% [9·5]) and decreased absolute neutrophil count (6·8 [3·0] × 109 cells per L to 3·6 [2·2] × 109 cells per L). Incidence rate ratios (IRR) comparing MTD with fixed-dose hydroxyurea indicate decreased vaso-occlusive episodes (0·60; 95% CI 0·52-0·70; p<0·0001), acute chest syndrome events (0·21; 0·13-0·33; p<0·0001), recurrent stroke events (0·27; 0·07-1·06; p=0·061), malaria infections (0·58; 0·46-0·72; p<0·0001), non-malarial infections (0·52; 0·46-0·58; p<0·0001), serious adverse events (0·42; 0·27-0·67; p<0·0001), and death (0·70; 0·25-1·97; p=0·50). Dose-limiting toxicity rates were similar between the fixed-dose (24·1 per 100 patient-years) and MTD phases (23·2 per 100 patient-years; 0·97; 0·70-1·35; p=0·86). Grade 3 and 4 adverse events were infrequent (18·5 per 100 patient-years) and included malaria infection, non-malarial infections, vaso-occlusive pain, and acute chest syndrome. Serious adverse events were uncommon (3·6 per 100 patient-years) and included malaria infections, parvovirus-associated anaemia, sepsis, and stroke, with no treatment-related deaths. INTERPRETATION: Hydroxyurea dose escalation to MTD with dose optimisation significantly improved clinical responses and treatment outcomes, without increasing toxicities in children with sickle cell anaemia in sub-Saharan Africa. FUNDING: US National Heart, Lung, and Blood Institute and Cincinnati Children's Research Foundation.

Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Persistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery. METHODS: PLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1-3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness. DISCUSSION: This trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients. TRIAL REGISTRATION: This trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021).

Cost Analysis of Bladder Catheterization After Pelvic Floor Surgery.

IMPORTANCE: Approximately 15-45% of female patients develop transient postoperative urinary retention (POUR) following pelvic reconstructive surgery. Catheter options for bladder drainage include transurethral indwelling catheter (TIC), intermittent self-catheterization (ISC), and suprapubic tube (SPT). Each strategy has risks and benefits; none have been shown to be clinically superior, and to date, no comprehensive comparative economic analysis has been published. OBJECTIVE: The objective of this study was to evaluate the cost of these different bladder catheterization strategies after transvaginal pelvic surgery. STUDY DESIGN: A Canadian universal single-payer (government funded) health system perspective was taken, and a decision tree model was constructed to evaluate the costs associated with each catheterization strategy over a 6-week horizon. Base-cases were set based on recently published clinical data of our institutions, 2 academic tertiary care centers, and based on systematic reviews and meta-analyses. Costs were established in consultation with process stakeholders, in addition to published values. RESULTS: The average cost calculated for management of transient POUR after outpatient pelvic reconstructive surgery was 150.69 CAD (median 154.86; interquartile range [IQR] 131.30-176.33) for TIC, 162.28 CAD (median 164.72; IQR 144.36-189.39) for ISC and 255.67 CAD (median 270.63; IQR 234.32-276.82) for SPT. In costing inpatient surgical data, the average cost calculated was 134.22 CAD (median 123.61; IQR 108.87-151.85) for TIC and 224.61 CAD (median 216.07; IQR 203.86-231.23) for SPT. CONCLUSION: TIC and ISC were found to be significantly less costly than SPT in managing transient POUR following transvaginal pelvic reconstructive surgery.

Recent Improvements in Attainment of the Hemoglobin A1c Target of ≤7.0% Among Adults with Type 1 Diabetes in Ontario: A Retrospective Cohort Study.

Aims: We evaluated attainment of the hemoglobin A1c (HbA1c) target of ≤7.0%, its temporal trends, and associated factors among adults with type 1 diabetes in Ontario, Canada, using administrative data. Methods: We conducted a retrospective cohort study, including Ontarians with type 1 diabetes ≥18 years old with ≥1 HbA1c test between April 1, 2012 (fiscal year 2013), and March 31, 2023. Generalized estimating equations were used to determine probabilities of meeting the HbA1c target, as well as associations between fiscal year and individual-, physician-, and system-level factors on odds of meeting the target. Results: Among 28,827 adults with type 1 diabetes [14,385 (49.9%) female, 17,998 (62.4%) pump users], with median age at index of 25 years [interquartile range (IQR) 18-37] and median diabetes duration of 12 years [6-18], there were 474,714 HbA1c tests [median 2/individual/year (IQR: 1-3)]. The model-estimated probability of meeting the HbA1c target of ≤7.0% was 22.1% (95% confidence interval, CI: 21.6 to 22.5) in 2013, remained stable until 2020, and increased to 34.7% (95% CI: 34.3 to 35.2) in 2023. The age- and sex-adjusted odds ratio for meeting the target in 2023 versus 2013 was 1.87 (95% CI: 1.79 to 1.96). Young adults (18-25 years), diabetic ketoacidosis, greater comorbidity, and receiving diabetes care from a nonspecialist physician were associated with reduced odds of meeting the HbA1c target. Conclusions: One-third of adults with type 1 diabetes in Ontario met the recommended HbA1c target of ≤7.0% in 2023, with improvement noted since 2021, which may be due to advanced technologies or effects of the COVID-19 pandemic.

Optimizing practices to prevent urinary tract infection after cystoscopy and urodynamics in women: A quality improvement study.

OBJECTIVE: The objective of this study was to reduce the incidence of urinary tract infection (UTI) in women undergoing outpatient cystoscopy and/or urodynamic studies (UDS) at our centre by identifying and then altering modifiable risk factors through an analysis of incidence variability among physicians. METHODS: This was a quality improvement study involving adult women undergoing outpatient cystoscopy and/or UDS at an academic tertiary urogynecology practice. Prophylactic practices for cystoscopy/UDS were surveyed and division and physician-specific UTI rates following cystoscopy/UDS were established. In consultation with key stakeholders, this delineated change concepts based on associations between prophylactic practices and UTI incidence, which were then implemented while monitoring counterbalance measures. RESULTS: Two "Plan-Do-Study-Act-Cycles" were conducted whereby 212 and 210 women were recruited, respectively. Change concepts developed and implemented were: (1) to perform routine urine cultures at the time of these outpatient procedures, and (2) to withhold routine prophylactic antibiotics for outpatient cystoscopy/UDS, except in patients with signs of cystitis. There was no change in the incidence of early presenting UTI (9.0% vs. 9.2%, p = 0.680), but there were significantly fewer antibiotic-related adverse events reported (8.5% vs. 1.5%, p = 0.001). There was no significant change in the total incidence of UTI rates between cycles (7.8% vs. 5.6%, p = 0.649). CONCLUSIONS: No specific strategies to decrease the incidence of UTI following outpatient cystoscopy/UDS were identified, however, risk factor-specific antibiotic prophylaxis, as opposed to universal antibiotic prophylaxis, did not increase UTI incidence.

Reducing transfusion utilization for children with sickle cell anemia in sub-Saharan Africa with hydroxyurea: Analysis from the phase I/II REACH trial.

Children with sickle cell anemia (SCA) in Africa frequently require transfusions for SCA complications. Despite limited blood supplies, strategies to reduce their transfusion needs have not been widely evaluated or implemented. We analyzed transfusion utilization in children with SCA before and during hydroxyurea treatment. REACH (Realizing Effectiveness Across Continents with Hydroxyurea, NCT01966731) is a longitudinal Phase I/II trial of hydroxyurea in children with SCA from Angola, Democratic Republic of Congo, Kenya, and Uganda. After enrollment, children had a two-month pre-treatment screening period followed by 6 months of fixed-dose hydroxyurea (15-20 mg/kg/day), 18 months of dose escalation, and then stable dosing at maximum tolerated dose (MTD). Characteristics associated with transfusions were analyzed with univariate and multivariable models. Transfusion incidence rate ratios (IRR) across treatment periods were calculated. Among 635 enrolled children with 4124 person-years of observation, 258 participants (40.4%) received 545 transfusions. The transfusion rate per 100 person-years was 43.2 before hydroxyurea, 21.7 on fixed-dose, 14.5 during dose escalation, and 10.8 on MTD. During MTD, transfusion incidence was reduced by 75% compared to pre-treatment (IRR 0.25, 95% confidence interval [CI] 0.18-0.35, p < .0001), and by 50% compared to fixed dose (IRR 0.50, 95% CI 0.39-0.63, p < .0001). Hydroxyurea at MTD decreases transfusion utilization in African children with SCA. If widely implemented, universal testing and hydroxyurea treatment at MTD could potentially prevent 21% of all pediatric transfusions administered in sub-Saharan Africa. Increasing hydroxyurea access for SCA should decrease the transfusion burden and increase the overall blood supply.

Understanding the incidence, duration, and severity of symptoms through daily symptom monitoring among frail and non-frail older patients receiving metastatic prostate cancer treatments.

INTRODUCTION: Older adults with metastatic prostate cancer (mPC) experience high symptom burden associated with treatment. Frailty may exacerbate treatment toxicity. The aim of this study was to explore short-term treatment toxicity in patients with metastatic prostate cancer. MATERIALS AND METHODS: Older adults with metastatic prostate cancer starting chemotherapy, androgen-receptor-axis targeted therapies, or radium-223 participated in a prospective, multicentre, observational study. Participants self-reported symptoms daily using the Edmonton Symptom Assessment System for one treatment cycle via internet or telephone. The most common moderate-to-severe symptoms (score≥4), their duration, and the proportion of participants who experienced improvements in symptom severity (score<4) after reporting moderate-to-severe symptoms at baseline were determined using descriptive statistics. Once-weekly symptom questionnaires were administered and analyzed using linear mixed effect models. Symptom incidence, duration, and frailty associations were assessed using t-tests and chi-square tests. RESULTS: Ninety participants completed the study (mean age=77 years [standard deviation=6.1], 42% frail [Vulnerable Elders Survey≥3]). The most common moderate-to-severe symptoms across cohorts were fatigue (46.8%), insomnia (42.9%), poor wellbeing (41.2%), pain (37.5%), and decreased appetite (37.1%). Poor wellbeing had a higher incidence in frail participants (62.5% in frail vs. 31.4% in non-frail, p=0.039). Symptom duration varied across cohorts and between frail and non-frail participants. Among participants who reported moderate-to-severe symptoms at baseline, no more than 15% improved in any symptom. There were statistically significant improvements in weekly symptoms for fatigue, decreased appetite, and insomnia in the chemotherapy cohort only. DISCUSSION: Limitations include a short follow-up duration, lack of a control group, and few radium-223 participants. Regular symptom monitoring can help clinicians understand temporal patterns and durations of symptoms and inform supportive care approaches.

The influence of drugs used for sedation during mechanical ventilation on respiratory pattern during unassisted breathing and assisted mechanical ventilation: a physiological systematic review and meta-analysis.

Background: Sedation management has a major impact on outcomes in mechanically ventilated patients, but sedation strategies do not generally consider the differential effects of different sedatives on respiration and respiratory pattern. A systematic review was undertaken to quantitatively summarize the known effects of different classes of drugs used for sedation on respiratory pattern during both spontaneous breathing and assisted mechanical ventilation. Methods: This was a systematic review and meta-analysis conducted using Ovid MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials up to June 2020 to retrieve studies that measured respiratory parameters before and after the administration of opioids, benzodiazepines, intravenous and inhaled anaesthetic agents, and other hypnotic agents (PROSPERO #CRD42020190017). A random-effects meta-analytic model was employed to estimate the mean percentage change in each of the respiratory indices according to medication exposure with and without mechanical ventilation. Risk of bias was assessed using the Cochrane risk of bias assessment tools. Findings: Fifty-one studies were included in the analysis. Risk of bias was generally deemed to be low for most studies. Respiratory rate decreased with the administration of opioids in both non-ventilated patients (18% decrease, 95% CI 12-24%) and ventilated patients (26% decrease, 95% CI 15-37%) and increased with inhaled anaesthetics in non-ventilated patients (83% increase, 95% CI 49-118%) and ventilated patients (50% increase, 28-72%). In non-ventilated patients, tidal volume decreased following administration of inhaled aesthetics (55% decrease, 95% CI 25-86%), propofol (36% decrease, 95% CI 20-52%), and benzodiazepines (28% decrease, 95% CI 17-40%); in patients receiving assisted mechanical ventilation, tidal volume was not significantly affected by sedation. Administration of other hypnotic agents was not associated with changes in respiratory rate or tidal volume. Interpretation: Different classes of drugs used for sedation exert differential effects on respiratory pattern, and this may influence weaning and outcomes in mechanically ventilated patients. Funding: This study did not receive any funding support.