Prognostic implications of volume status assessed by blood volume analysis in ambulatory heart failure.

The prognostic implications of intravascular volume status assessed by blood volume analysis (BVA) in ambulatory heart failure (HF) remain uncertain. The incremental benefits of assessing volume status, beyond the well-established filling pressures, in predicting HF outcomes are unknown.

A Survey to Assess the Current Status of Structured Benefit-Risk Assessment in the Global Drug and Medical Device Industry.

BACKGROUND: This industry survey was conducted to gain insight into the ways structured Benefit-Risk assessment (sBRA) of medical products is approached across drug or medical device developing companies, including frameworks and methods that are currently used and areas where future work is being planned. METHODS: A survey containing 28 questions covering five key areas of sBRA was set-up and shared with representatives from the participating companies. Each company was asked to complete a single survey response including inputs across the company's multidisciplinary key representatives involved in benefit-risk assessment. RESULTS: Of the 26 participating companies, 21 (81%) are conducting sBRA. Considering these 21 qualitative frameworks were used by almost every company (19, 90%), while only 12 (57%) have used a quantitative method. Many companies have sBRA training (17, 81%), document templates (16,76%), Standard Operating Procedures (SOPs)/checklists (13, 62%), and /or best practice manuals/examples (12,57%) available. Considering all 26 companies Software tools (15, 58%) and BR planning documents (11,42%) were identified as areas into which many companies intend to put effort. CONCLUSIONS: The industry survey confirmed a wide usage of sBRA by many companies involved in research and development. Nevertheless, sBRA is evolving and several future opportunities like the implementation of visualization tools were identified by the representatives of the pharmaceutical companies. Finally, challenges like the cross-functional comprehension of the added value of sBRA are still seen.

Reference values for leg effort during incremental cycle ergometry in non-trained healthy men and women, aged 19-85.

Heightened sensation of leg effort contributes importantly to poor exercise tolerance in patient populations. We aim to provide a sex- and age-adjusted frame of reference to judge symptom's normalcy across progressively higher exercise intensities during incremental exercise. Two-hundred and seventy-five non-trained subjects (130 men) aged 19-85 prospectively underwent incremental cycle ergometry. After establishing centiles-based norms for Borg leg effort scores (0-10 category-ratio scale) versus work rate, exponential loss function identified the centile that best quantified the symptom's severity individually. Peak O2 uptake and work rate (% predicted) were used to threshold gradually higher symptom intensity categories. Leg effort-work rate increased as a function of age; women typically reported higher scores at a given age, particularly in the younger groups (p < 0.05). For instance, "heavy" (5) scores at the 95th centile were reported at ~200 W (<40 years) and ~90 W (≥70 years) in men versus ~130 W and ~70 W in women, respectively. The following categories of leg effort severity were associated with progressively lower exercise capacity: ≤50th ("mild"), >50th to <75th ("moderate"), ≥75th to <95th ("severe"), and ≥ 95th ("very severe") (p < 0.05). Although most subjects reporting peak scores <5 were in "mild" range, higher scores were not predictive of the other categories (p > 0.05). This novel frame of reference for 0-10 Borg leg effort, which considers its cumulative burden across increasingly higher exercise intensities, might prove valuable to judging symptom's normalcy, quantifying its severity, and assessing the effects of interventions in clinical populations.

Granuloprival cerebellar cortical degeneration in a Yorkshire Terrier and Lagotto Romagnolo dog.

Granuloprival degeneration is an uncommon form of cerebellar cortical degeneration (CCD). A 3-month-old Yorkshire Terrier and a 7-month-old Lagotto Romagnolo dog were presented with a history of progressive cerebellar dysfunction including wide-based stance, cerebellar ataxia, intention tremors, and loss of menace response despite normal vision. Magnetic resonance imaging of the brain identified marked diffuse decrease of the cerebellum size. Euthanasia was performed in both cases because of progression of clinical signs. Histopathological examination identified marked diffuse thinning of the granular cell layer with almost complete loss of the granular cell neurons, providing a definitive diagnosis of granuloprival CCD. Granuloprival CCD should be considered as a differential diagnosis in Yorkshire Terrier and Lagotto Romagnolo dogs with post-natal progressive clinical signs of cerebellar dysfunction.

Advancing Community Care and Access to Follow-up After Acute Kidney Injury Hospitalization: Design of the AFTER AKI Randomized Controlled Trial.

Background: Acute kidney injury (AKI) is a common complication among hospitalized patients with long-term implications including chronic kidney disease (CKD). Although models are available to predict the risk of advanced CKD after AKI, there is limited evidence regarding follow-up for patients with AKI after hospital discharge, resulting in variable follow-up care. A risk-stratified follow-up approach may improve appropriateness and efficiency of management for CKD among patients at risk of declining kidney function following AKI. Objective: The objective was to compare and evaluate the use of a risk-stratified approach to follow-up care vs usual care for patients with AKI after hospital discharge. Design: This study was a pragmatic randomized controlled trial. Setting: This study was conducted in 2 large urban hospitals in Alberta, Canada. Patients: Hospitalized patients with AKI (KDIGO stage 2 or 3) not previously under the care of a nephrologist, expected to survive greater than 90 days being discharged home. Measurements: We will evaluate whether guideline-recommended CKD care processes are initiated within 90 days, including statin use, angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB) use in those with proteinuria or diabetes, and nephrologist follow-up if sustained eGFR <30 mL/min/1.73 m2. We will also assess the feasibility of recruitment and the proportion of patients completing the recommended blood and urine tests at 90 days. Methods: Patients with AKI will be enrolled and randomized near the time of hospital discharge. In the intervention group, low risk patients will receive information regarding AKI, medium risk patients will additionally receive follow-up guidance sent to their primary care physician, and high-risk patients will additionally receive follow-up with a nephrologist. Participants in the intervention and usual care group will receive a requisition for urine testing and bloodwork at 90 days following hospital discharge. Telephone follow-up will be conducted for all study participants at 90 days and 1 year after hospital discharge. Bivariate tests of association will be conducted to evaluate group differences at the follow-up time points. Limitations: We expect there may be challenges with recruitment due to the significant co-existence of comorbidity in this population. Conclusions: If the trial shows a positive effect on these processes for kidney care, it will inform larger-scale trial to determine whether this intervention reduces the incidence of long-term clinical adverse events, including CKD progression, cardiovascular events, and mortality following hospitalization with AKI.

Contexte: L'insuffisance rénale aiguë (IRA) est une complication fréquente chez les patients hospitalisés qui peut avoir des conséquences à long terme, notamment l'insuffisance rénale chronique (IRC). Bien que des modèles de prédiction du risque d'IRC avancée après un épisode d'IRA soient disponibles, peu de données existent sur le suivi des patients atteints d'IRA après leur sortie de l'hôpital, ce qui se traduit par une variabilité dans les soins de suivi. Une approche de suivi stratifiée selon le risque d'IRC peut améliorer la qualité et l'efficacité de la prise en charge de l'IRC chez les patients dont la fonction rénale risque de se détériorer après un épisode d'IRA. Objectifs: Évaluer l'utilisation d'une approche de suivi post-hospitalisation stratifiée selon le risque d'IRC chez les patients atteints d'IRA et la comparer aux soins habituels. Conception: Essai contrôlé randomisé pragmatique. Cadre: Deux grands hôpitaux urbains en Alberta (Canada). Sujets: Patients hospitalisés avec une IRA (stade KDIGO 2 ou 3) qui n'étaient pas suivis auparavant par un néphrologue et dont on prévoyait la survie au-delà de 90 jours après leur sortie de l'hôpital. Mesures: Nous évaluerons si, dans les 90 jours suivant le congé, les soins d'IRC habituels recommandés par les lignes directrices seront amorcés, c'est-à-dire l'utilisation de statines, l'utilisation d'IECA/ARA chez les patients souffrant de protéinurie ou de diabète, et le suivi avec un néphrologue pour les patients avec un DFGe inférieur à 30 ml/min/1,73 m2 de façon soutenue. Nous évaluerons également la faisabilité du recrutement et la proportion de patients qui auront effectué les analyses sanguines et urinaires recommandées à 90 jours. Méthodologie: Les patients atteints d'IRA seront recrutés et randomisés au moment de leur sortie de l'hôpital. Dans le groupe d'intervention, les patients présentant un faible risque d'évolution recevront de l'information sur l'IRA, les patients présentant un risque moyennement élevé recevront en plus des conseils de suivi envoyés à leur médecin de premier recours, et les patients présentant un risque élevé feront également l'objet d'un suivi avec un néphrologue. Les participants des groupes intervention et soins habituels recevront une requête pour des analyses de sang et d'urine 90 jours après la sortie de l'hôpital. Un suivi téléphonique sera effectué auprès de tous les participants à l'étude 90 jours et un an après la sortie de l'hôpital. Des tests d'association bivariés seront effectués pour évaluer les différences entre les groupes aux points temporels de suivi. Limites: Nous nous attendons à ce que le recrutement soit difficile, considérant l'importance des comorbidités dans cette population. Conclusion: Si l'essai montre un effet positif sur ces processus de soins rénaux, il informera un essai à plus grande échelle visant à déterminer si cette intervention réduit l'incidence des événements cliniques indésirables à long terme, notamment la progression de l'IRC, les événements cardiovasculaires et la mortalité après une hospitalisation avec épisode d'IRA.

Autochthonous Ascariasis, Mississippi, USA.

We describe a case of a 2-year-old child who expelled a single adult female Ascaris lumbricoides worm. The patient is from a rural county in Mississippi, USA, with no reported travel outside of the United States. The caregivers in the home practice good sanitation. Exposure to domestic pigs is the likely source of infection.

Investigating the associations between lumbar paraspinal muscle health and age, BMI, sex, physical activity, and back pain using an automated computer-vision model: A UK Biobank study.

BACKGROUND CONTEXT: The role of lumbar paraspinal muscle health in back pain (BP) is not straightforward. Challenges in this field have included the lack of tools and large, heterogenous datasets to interrogate the association between muscle health and BP. Computer-vision models have been transformative in this space, enabling the automated quantification of muscle health and the processing of large datasets. PURPOSE: To investigate the associations between lumbar paraspinal muscle health and age, sex, BMI, physical activity, and BP in a large, heterogenous dataset using an automated computer-vision model. DESIGN: Cross-sectional study. PATIENT SAMPLE: Participants from the UK Biobank with abdominal Dixon fat-water MRI (N=9,564) were included (41.8% women, mean [SD] age: 63.5 [7.6] years, BMI: 26.4 [4.1] kg/m2) of whom 6,953 reported no pain, 930 acute BP, and 1,681 chronic BP. OUTCOME MEASURES: Intramuscular fat (IMF) and average cross-sectional area (aCSA) were automatically derived using a computer-vision model for the left and right lumbar multifidus (LM), erector spinae (ES), and psoas major (PM) from the L1 to L5 vertebral levels. METHODS: Two-tailed partial Pearson correlations were generated for each muscle to assess the relationships between the muscle measures (IMF and aCSA) and age (controlling for BMI, sex, and physical activity), BMI (controlling for age, sex, and physical activity), and physical activity (controlling for age, sex, and BMI). One-way ANCOVA was used to identify sex differences in IMF and aCSA for each muscle while controlling for age, BMI, and physical activity. Similarly, one-way ANCOVA was used to identify between-group differences (no pain, acute BP, and chronic BP) for each muscle and along the superior-inferior expanse of the lumbar spine while controlling for age, BMI, sex, and physical activity (α=0.05). RESULTS: Females had higher IMF (LM mean difference [MD]=11.1%, ES MD=10.2%, PM MD=0.3%, p<.001) and lower aCSA (LM MD=47.6 mm2, ES MD=350.0 mm2, PM MD=321.5 mm2, p<.001) for all muscles. Higher age was associated with higher IMF and lower aCSA for all muscles (r≥0.232, p<.001) except for LM and aCSA (r≤0.013, p≥.267). Higher BMI was associated with higher IMF and aCSA for all muscles (r≥0.174, p<.001). Higher physical activity was associated with lower IMF and higher aCSA for all muscles (r≥0.036, p≤.002) except for LM and aCSA (r≤0.010, p≥.405). People with chronic BP had higher IMF and lower aCSA than people with no pain (IMF MD≤1.6%, aCSA MD≤27.4 mm2, p<.001) and higher IMF compared to acute BP (IMF MD≤1.1%, p≤.044). The differences between people with BP and people with no pain were not spatially localized to the inferior lumbar levels but broadly distributed across the lumbar spine. CONCLUSIONS: Paraspinal muscle health is associated with age, BMI, sex, and physical activity with the exception of the association between LM aCSA and age and physical activity. People with BP (chronic>acute) have higher IMF and lower aCSA than people reporting no pain. The differences were not localized but broadly distributed across the lumbar spine. When interpreting measures of paraspinal muscle health in the research or clinical setting, the associations with age, BMI, sex, and physical activity should be considered.

Managing Medications During "Sick Days" in Patients With Diabetes, Kidney, and Cardiovascular Conditions: A Theory-informed Approach to Intervention Design and Implementation.

OBJECTIVES: Our aim in this work was to: 1) explore barriers and enablers to patient and health-care provider (HCP) behaviours related to sick-day medication guidance (SDMG), 2) identify theory-informed strategies to advise SDMG intervention design, and 3) obtain perspectives on an eHealth tool for this purpose. METHODS: A qualitative descriptive study using qualitative conventional content analysis was undertaken. Interviews and focus groups were held with patients and HCPs from January 2021 to April 2022. Data were analyzed using the Behaviour Change Wheel and Theoretical Domains Framework to inform intervention design. RESULTS: Forty-eight people (20 patients, 13 pharmacists, 12 family physicians, and 3 nurse practitioners) participated in this study. Three interventions were designed to address the identified barriers and enablers: 1) prescriptions provided by a community-based care provider, 2) pharmacists adding a label to at-risk medications, and 3) built-in prompts for prescribing and dispensing software. Most participants accepted the concept of an eHealth tool and identified pharmacists as the ideal point-of-care provider. Challenges for an eHealth tool were raised, including credibility, privacy of data, medical liability, clinician remuneration and workload impact, and equitable access to use of the tool. CONCLUSIONS: Patients and HCPs endorsed non-technology and eHealth innovations as strategies to aid in the delivery of SDMG. These findings can guide the design of future theory-informed SDMG interventions.

The effect of goal-directed fluid therapy on delayed graft function in kidney transplant recipients: A systematic review and meta-analysis.

Delayed graft function (DGF) is a common post-operative complication with potential long-term sequelae for many kidney transplant recipients, and hemodynamic factors and fluid status play a role. Fixed perioperative fluid infusions are the standard of care, but more recent evidence in the non-transplant population has suggested benefit with goal-directed fluid strategies based on hemodynamic targets. We searched MEDLINE, EMBASE, Cochrane Controlled Trials Registry and Google Scholar through December 2022 for randomized controlled trials comparing risk of DGF between goal-directed and conventional fluid therapy in adults receiving a living or deceased donor kidney transplant. Effect estimates were reported with odds ratios (OR) and pooled using random effects meta-analysis. We identified 4 studies (205 participants) that met the inclusion criteria. The use of goal-directed fluid therapy had no significant effect on DGF (OR 1.37 95% CI, 0.34-5.6; p = 0.52; I2 = 0.11). Subgroup analysis examining effects among deceased and living kidney donation did not reveal significant differences in the effects of fluid strategy on DGF between subgroups. Overall, the strength of the evidence for goal-directed versus conventional fluid therapy to reduce DGF was of low certainty. Our findings highlight the need for larger trials to determine the effect of goal-directed fluid therapy on this patient-centered outcome.

Beyond Spirometry: Linking Wasted Ventilation to Exertional Dyspnea in the Initial Stages of COPD.

Exertional dyspnea, a key complaint of patients with chronic obstructive pulmonary disease (COPD), ultimately reflects an increased inspiratory neural drive to breathe. In non-hypoxemic patients with largely preserved lung mechanics - as those in the initial stages of the disease - the heightened inspiratory neural drive is strongly associated with an exaggerated ventilatory response to metabolic demand. Several lines of evidence indicate that the so-called excess ventilation (high ventilation-CO2 output relationship) primarily reflects poor gas exchange efficiency, namely increased physiological dead space. Pulmonary function tests estimating the extension of the wasted ventilation and selected cardiopulmonary exercise testing variables can, therefore, shed unique light on the genesis of patients' out-of-proportion dyspnea. After a succinct overview of the basis of gas exchange efficiency in health and inefficiency in COPD, we discuss how wasted ventilation translates into exertional dyspnea in individual patients. We then outline what is currently known about the structural basis of wasted ventilation in "minor/trivial" COPD vis-à-vis the contribution of emphysema versus a potential impairment in lung perfusion across non-emphysematous lung. After summarizing some unanswered questions on the field, we propose that functional imaging be amalgamated with pulmonary function tests beyond spirometry to improve our understanding of this deeply neglected cause of exertional dyspnea. Advances in the field will depend on our ability to develop robust platforms for deeply phenotyping (structurally and functionally), the dyspneic patients showing unordinary high wasted ventilation despite relatively preserved FEV1.

Physiological Characterization of Preserved Ratio Impaired Spirometry in the CanCOLD Study: Implications for Exertional Dyspnea and Exercise Intolerance.

RATIONALE: It is increasingly recognized that adults with preserved ratio impaired spirometry (PRISm) are prone to increased morbidity. However, the underlying pathophysiological mechanisms are unknown. OBJECTIVES: Evaluate the mechanisms of increased dyspnea and reduced exercise capacity in PRISm. METHODS: We completed a cross-sectional analysis of the CanCOLD population-based study. We compared physiological responses in 59 participants meeting PRISm spirometric criteria (post-bronchodilator FEV1<80% predicted and FEV1/FVC≥0.7), 264 controls, and 170 ever-smokers with chronic obstructive pulmonary disease (COPD), at rest and during cardiopulmonary exercise testing (CPET). MEASUREMENTS AND MAIN RESULTS: PRISm had lower total lung, vital and inspiratory capacities than controls (all p<0.05), and minimal small airway, pulmonary gas-exchange, and radiographic parenchymal lung abnormalities. Compared with control, PRISm had higher dyspnea/oxygen uptake [V̇O2] ratio at peak exercise (4.0±2.2vs2.9±1.9, Borg units/L/min, p<0.001) and lower V̇O2peak (74±22vs96±25% predicted, p<0.001). At standardized submaximal work rates, PRISm had greater tidal volume/inspiratory capacity (VT%IC, p<0.001), reflecting inspiratory mechanical constraint. In contrast to PRISm, COPD had characteristic small airways dysfunction, dynamic hyperinflation, and pulmonary gas-exchange abnormalities. Despite these physiological differences between the 3 groups, the relationship between increasing dyspnea and VT%IC during CPET was similar. Resting IC significantly correlated with V̇O2peak (r=0.65, p<0.001) in the entire sample, even after adjusting for airflow limitation, gas-trapping and diffusing capacity. CONCLUSION: In PRISm, lower exercise capacity and higher exertional dyspnea than healthy controls were mainly explained by lower resting lung volumes and earlier onset of dynamic inspiratory mechanical constraints at relatively low work rates.

Recovery of kidney function after acute kidney disease-a multi-cohort analysis.

BACKGROUND: There are no consensus definitions for evaluating kidney function recovery after acute kidney injury (AKI) and acute kidney disease (AKD), nor is it clear how recovery varies across populations and clinical subsets. We present a federated analysis of four population-based cohorts from Canada, Denmark and Scotland, 2011-18. METHODS: We identified incident AKD defined by serum creatinine changes within 48 h, 7 days and 90 days based on KDIGO AKI and AKD criteria. Separately, we applied changes up to 365 days to address widely used e-alert implementations that extend beyond the KDIGO AKI and AKD timeframes. Kidney recovery was based on resolution of AKD and a subsequent creatinine measurement below 1.2× baseline. We evaluated transitions between non-recovery, recovery and death up to 1 year; within age, sex and comorbidity subgroups; between subset AKD definitions; and across cohorts. RESULTS: There were 464 868 incident cases, median age 67-75 years. At 1 year, results were consistent across cohorts, with pooled mortalities for creatinine changes within 48 h, 7 days, 90 days and 365 days (and 95% confidence interval) of 40% (34%-45%), 40% (34%-46%), 37% (31%-42%) and 22% (16%-29%) respectively, and non-recovery of kidney function of 19% (15%-23%), 30% (24%-35%), 25% (21%-29%) and 37% (30%-43%), respectively. Recovery by 14 and 90 days was frequently not sustained at 1 year. Older males and those with heart failure or cancer were more likely to die than to experience sustained non-recovery, whereas the converse was true for younger females and those with diabetes. CONCLUSION: Consistently across multiple cohorts, based on 1-year mortality and non-recovery, KDIGO AKD (up to 90 days) is at least prognostically similar to KDIGO AKI (7 days), and covers more people. Outcomes associated with AKD vary by age, sex and comorbidities such that older males are more likely to die, and younger females are less likely to recover.

Processes of Care After Hospital Discharge for Survivors of Acute Kidney Injury: A Population-Based Cohort Study.

RATIONALE & OBJECTIVE: Survivors of acute kidney injury (AKI) are at high risk of adverse outcomes. Monitoring of kidney function, screening for proteinuria, use of statins and renin-angiotensin-aldosterone system (RAAS) inhibitors, and nephrology follow-up among survivors have not been fully characterized. We examined these processes of care after discharge in survivors of hospitalized AKI. STUDY DESIGN: Population-based retrospective cohort study. SETTING & PARTICIPANTS: Adults in Alberta, Canada, admitted to the hospital between 2009 and 2017, then followed from their discharge date until 2019 for a median follow-up of 2.7 years. EXPOSURE: Hospital-acquired AKI diagnostically conforming to Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria for stage 2 or stage 3 disease, or the need for acute dialysis. OUTCOME: Outcomes after hospital discharge included the proportion of participants who had evaluation of kidney function, were seen by a specialist or general practitioner, and received postdischarge prescriptions for recommended medications for chronic kidney disease (CKD). ANALYTICAL APPROACH: Cumulative incidence curves to characterize the proportion of participants who received each process of care outcome within the first 90 days and subsequent 1-year follow-up period after hospital discharge. To avoid risks associated with multiple hypothesis testing, differences were not statistically compared across groups. RESULTS: The cohort (n=23,921) included 50.2% men (n=12,015) with a median age of 68.1 [IQR, 56.9-78.8] years. Within 90 days after discharge, 21.2% and 8.6% of patients with and without pre-existing CKD, respectively, were seen by a nephrologist; 60.1% of AKI survivors had at least 1 serum creatinine measured, but only 25.5% had an assessment for albuminuria within 90 days after discharge; 52.7% of AKI survivors with pre-existing CKD, and 51.6% with de novo CKD were prescribed a RAAS inhibitor within 4-15 months after discharge. LIMITATIONS: Retrospective data were collected as part of routine clinical care. CONCLUSIONS: The proportion of patients receiving optimal care after an episode of AKI in Alberta was low and may represent a target for improving long-term outcomes for this population. PLAIN-LANGUAGE SUMMARY: A study in Alberta, Canada, examined the care received by patients with acute kidney disease (AKI) during hospitalization and after discharge between 2007 and 2019. The results showed that a low proportion of patients with moderate to severe AKI were seen by a kidney specialist during hospitalization or within 90 days after discharge. Fewer than 25% of AKI patients had their kidney function monitored with both blood and urine tests within 90 days of discharge. Additionally, about half of AKI survivors with chronic kidney disease (CKD) were prescribed guideline recommended medications for CKD within 15 months after discharge. There is potential to improve health care delivery to these patients both in hospital and after hospital discharge.

Unsupervised item response theory models for assessing sample heterogeneity in patient-reported outcomes measures.

PURPOSE: Unsupervised item-response theory (IRT) models such as polytomous IRT based on recursive partitioning (IRTrees) and mixture IRT (MixIRT) models can be used to assess differential item functioning (DIF) in patient-reported outcome measures (PROMs) when the covariates associated with DIF are unknown a priori. This study examines the consistency of results for IRTrees and MixIRT models. METHODS: Data were from 4478 individuals in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease registry who received cardiac angiography in Alberta, Canada, and completed the Hospital Anxiety and Depression Scale (HADS) depression subscale items. The partial credit model (PCM) based on recursive partitioning (PCTree) and mixture PCM (MixPCM) were used to identify covariates associated with differential response patterns to HADS depression subscale items. Model covariates included demographic and clinical characteristics. RESULTS: The median (interquartile range) age was 64.5(15.7) years, and 3522(78.5%) patients were male. The PCTree identified 4 terminal nodes (subgroups) defined by smoking status, age, and body mass index. A 3-class PCM fits the data well. The MixPCM latent classes were defined by age, disease indication, smoking status, comorbid diabetes, congestive heart failure, and chronic obstructive pulmonary disease. CONCLUSION: PCTree and MixPCM were not consistent in detecting covariates associated with differential interpretations of PROM items. Future research will use computer simulations to assess these models' Type I error and statistical power for identifying covariates associated with DIF.

Response shift in coronary artery disease.

PURPOSE: Patients with coronary artery disease (CAD) experience significant angina symptoms and lifestyle changes. Revascularization procedures can result in better patient-reported outcomes (PROs) than optimal medical therapy (OMT) alone. This study evaluates the impact of response shift (RS) on changes in PROs of patients with CAD across treatment strategies. METHODS: Data were from patients with CAD in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease (APPROACH) registry who completed the 16-item Canadian version of the Seattle Angina Questionnaire at 2 weeks and 1 year following a coronary angiogram. Multi-group confirmatory factor analysis (MG-CFA) was used to assess measurement invariance across treatment groups at week 2. Longitudinal MG-CFA was used to test for RS according to receipt of coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or optimal medical therapy (OMT) alone. RESULTS: Of the 3116 patients included in the analysis, 443 (14.2%) received CABG, 2049(65.8%) PCI, and the remainder OMT alone. The MG-CFA revealed a partial-strong invariance across the treatment groups at 2 weeks (CFI = 0.98, RMSEA [90% CI] = 0.05 [0.03, 0.06]). Recalibration RS was detected on the Angina Symptoms and Burden subscale and its magnitude in the OMT, PCI, and CABG groups were 0.32, 0.28, and 0.53, respectively. After adjusting for RS effects, the estimated target changes were largest in the CABG group and negligible in the OMT group. CONCLUSION: Adjusting for RS is recommended in studies that use SAQ-CAN to assess changes in patients with CAD who have received revascularization versus OMT alone.

Nurse Practitioner Care Compared with Primary Care or Nephrologist Care in Early CKD.

BACKGROUND: Early interventions in CKD have been shown to improve health outcomes; however, gaps in access to nephrology care remain common. Nurse practitioners can improve access to care; however, the quality and outcomes of nurse practitioner care for CKD are uncertain. METHODS: In this propensity score-matched cohort study, patients with CKD meeting criteria for nurse practitioner care were matched 1:1 on their propensity scores for ( 1 ) nurse practitioner care versus primary care alone and ( 2 ) nurse practitioner versus nephrologist care. Processes of care were measured within 1 year after cohort entry, and clinical outcomes were measured over 5 years of follow-up and compared between propensity score-matched groups. RESULTS: A total of 961 (99%) patients from the nurse practitioner clinic were matched on their propensity score to 961 (1%) patients receiving primary care only while 969 (100%) patients from the nurse practitioner clinic were matched to 969 (7%) patients receiving nephrologist care. After matching to patients receiving primary care alone, those receiving nurse practitioner care had greater use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (82% versus 79%; absolute differences [ADs] 3.4% [95% confidence interval, 0.0% to 6.9%]) and statins (75% versus 66%; AD 9.7% [5.8% to 13.6%]), fewer prescriptions of nonsteroidal anti-inflammatory drugs (10% versus 17%; AD -7.2% [-10.4% to -4.2%]), greater eGFR and albuminuria monitoring, and lower rates of all-cause hospitalization (34.1 versus 43.3; rate difference -9.2 [-14.7 to -3.8] per 100 person-years) and all-cause mortality (3.3 versus 6.0; rate difference -2.7 [-3.6 to -1.7] per 100 person-years). When matched to patients receiving nephrologist care, those receiving nurse practitioner care were also more likely to be prescribed angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and statins, with no difference in the risks of experiencing adverse clinical outcomes. CONCLUSIONS: Nurse practitioner care for patients with CKD was associated with better guideline-concordant care than primary care alone or nephrologist care, with clinical outcomes that were better than or equivalent to primary care alone and similar to those with care by nephrologists. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_12_08_CJN0000000000000305.mp3.

Variations in Incidence and Prognosis of Stage 4 CKD Among Adults Identified Using Different Algorithms: A Population-Based Cohort Study.

RATIONALE & OBJECTIVE: Clinical guidelines define chronic kidney disease (CKD) as abnormalities of kidney structure or function for>3 months. Assessment of the duration criterion may be implemented in different ways, potentially impacting estimates of disease incidence or prevalence in the population, individual diagnosis, and treatment decisions, especially for more severe cases. We investigated differences in incidence and prognosis of CKD stage G4 identified by 1 of 4 algorithms. STUDY DESIGN: Population-based cohort study in Alberta, Canada. SETTING & PARTICIPANTS: Residents>18 years old with incident CKD stage G4 (eGFR 15-29mL/min/1.73m2) diagnosed between April 1, 2015, and March 31, 2018, based on administrative and laboratory data. EXPOSURE: Four outpatient eGFR-based algorithms, increasing in stringency, for defining cohorts with CKD G4 were evaluated: (1) a single test, (2) first eGFR<30mL/min/1.73m2 and a second eGFR 15-29mL/min/1.73m2 measured>90 days apart (2 tests), (3) ≥2 eGFR measurements of<30mL/min/1.73m2 sustained for>90 days (qualifying period) and the last eGFR in the qualifying period of 15-29mL/min/1.73m2 (relaxed sustained), and (4) ≥2 consecutive measurements of 15-29mL/min/1.73m2 for>90 days (rigorous sustained). OUTCOME: Time to the earliest of death, eGFR improvement (a sustained increase in eGFR to≥30mL/min/1.73m2 for>90 days and>25% increase from the index eGFR), or kidney failure. ANALYTICAL APPROACH: For each of the 4 cohorts, incidence rates and event-specific cumulative incidence functions at 1 year from cohort entry were estimated. RESULTS: The incidence rates of CKD G4 decreased as algorithms became more stringent, from 190.7 (single test) to 79.9 (rigorous sustained) per 100,000 person-years. The 2 cohorts based on sustained reductions in eGFR were of comparable size and 1-year event-specific probabilities. The 2 cohorts based on a single test and a 2-test sequence were larger and experienced higher probabilities of eGFR improvement. LIMITATIONS: A short follow-up period of 1 year and a predominantly White population. CONCLUSIONS: The use of more stringent algorithms for defining CKD G4 results in substantially lower estimates of disease incidence, the identification of a group with a lower probability of eGFR improvement, and a higher risk of kidney failure. These findings can inform implementation decisions of disease definitions in clinical reporting systems and research studies. PLAIN-LANGUAGE SUMMARY: Although guidelines recommend>3 months to define chronic kidney disease (CKD), the methods for defining specific stages, particularly G4 (eGFR 15-29mL/min/1.73m2) when referral to nephrology services is recommended, have been implemented differently across studies and surveillance programs. We studied differences in incidence and prognosis of CKD G4 cohorts identified by 4 algorithms using administrative and outpatient laboratory databases in Alberta, Canada. We found that, compared with a single-test definition, more stringent definitions resulted in a lower disease incidence and identified a group with worse short-term kidney outcomes. These findings highlight the impact of the choice of algorithm used to define CKD G4 on disease burden estimates at the population level, on individual prognosis, and on treatment/referral decisions.

Physician Variation and the Impact of Payment Model in Cardiac Imaging.

BACKGROUND: The influence of fee-for-service reimbursement on cardiac imaging has not been compared with other payment models. Furthermore, variation in ordering practices is not well understood. METHODS AND RESULTS: This retrospective, population-based cohort study using linked administrative data from Alberta, Canada included adults with chronic heart disease (atrial fibrillation, coronary artery disease, and heart failure) seen by cardiac specialists for a new outpatient consultation April 2012 to December 2018. Generalized linear mixed-effects models estimated the association of payment model (including the ability to bill to interpret imaging tests) and the use of cardiac imaging and quantified variation in cardiac imaging. Among 31 685 adults seen by 308 physicians at 136 sites, patients received an observed mean of 0.67 (95% CI, 0.67-0.68) imaging tests per consultation. After adjustment, patients seeing fee-for-service physicians had 2.07 (95% CI, 1.68-2.54) and fee-for-service physicians with ability to interpret had 2.87 (95% CI, 2.16-3.81) times the rate of receiving a test than those seeing salaried physicians. Measured patient, physician, and site effects accounted for 31% of imaging variation and, following adjustment, reduced unexplained site-level variation 40% and physician-level variation 29%. CONCLUSIONS: We identified substantial variation in the use of outpatient cardiac imaging related to physician and site factors. Physician payment models have a significant association with imaging use. Our results raise concern that payment models may influence cardiac imaging practice. Similar methods could be applied to identify the source and magnitude of variation in other health care processes and outcomes.

Split-GFP lamin as a tool for studying C. elegans LMN-1 dynamics in vivo.

We engineered a fluorescent fusion protein of C. elegans lamin, by fusing the eleventh beta strand of GFP to the N-terminus of LMN-1 at the endogenous lmn-1 locus. When co-expressed with GFP1-10, GFP11::LMN-1 was observed at the nuclear periphery of a wide variety of somatic cells. Homozygous gfp11::lmn-1 animals had normal numbers of viable embryos. However, the gfp11::lmn-1 animals had a mild swimming defect. While not completely functional, the GFP11::LMN-1 strain is more healthy than other published fluorescent LMN-1 lines, making it a valuable reagent for studying lamins.