IMPORTANCE Hip fractures in older adults are serious injuries that result in disability, higher rates of illness and death, and a substantial strain on health care resources. High-quality evidence... Show moreIMPORTANCE Hip fractures in older adults are serious injuries that result in disability, higher rates of illness and death, and a substantial strain on health care resources. High-quality evidence to improve hip fracture care regarding the surgical approach of hemiarthroplasty is lacking. OBJECTIVE To compare 6-month outcomes of the posterolateral approach (PLA) and direct lateral approach (DLA) for hemiarthroplasty in patients with acute femoral neck fracture. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized clinical trial (RCT) comparing DLA and PLA was performed alongside a natural experiment (NE) at 14 centers in the Netherlands. Patients aged 18 years or older with an acute femoral neck fracture were included, with or without dementia. Secondary surgery of the hip, pathological fractures, or patients with multitrauma were excluded. Recruitment took place between February 2018 and January 2022. Treatment allocation was random or pseudorandom based on geographical location and surgeon preference. Statistical analysis was performed from July 2022 to September 2022. EXPOSURE Hemiarthroplasty using PLA or DLA. MAIN OUTCOME AND MEASURES The primary outcome was health-related quality of life 6 months after surgery, quantified with the EuroQol Group 5-Dimension questionnaire (EQ-5D-5L). Secondary outcomes included dislocations, fear of falling and falls, activities of daily living, pain, and reoperations. To improve generalizability, a novel technique was used for data fusion of the RCT and NE. RESULTS A total of 843 patients (542 [64.3%] female; mean [SD] age, 82.2 [7.5] years) participated, with 555 patients in the RCT (283 patients in the DLA group; 272 patients in the PLA group) and 288 patients in the NE (172 patients in the DLA group; 116 patients in the PLA group). In the RCT, mean EQ-5D-5L utility scores at 6 months were 0.50 (95% CI, 0.45-0.55) after DLA and 0.49 (95% CI, 0.44-0.54) after PLA, with 77% completeness. The between-group difference (-0.04 [95% CI, -0.11 to 0.04]) was not statistically significant nor clinically meaningful. Most secondary outcomes were comparable between groups, but PLA was associated with more dislocations than DLA (RCT: 15 of 272 patients [5.5%] in PLA vs 1 of 283 patients [0.4%] in DLA; NE: 6 of 113 patients [5.3%]) in PLA vs 2 of 175 patients [1.1%] in DLA). Data fusion resulted in an effect size of 0.00 (95% CI, -0.04 to 0.05) for the EQ-5D-5L and an odds ratio of 12.31(95% CI, 2.77 to 54.70) for experiencing a dislocation after PLA. CONCLUSIONS AND RELEVANCE This combined RCT and NE found that among patients treated with a cemented hemiarthroplasty after an acute femoral neck fracture, PLA was not associated with a better quality of life than DLA. Rates of dislocation and reoperation were higher after PLA. Randomized and pseudorandomized data yielded similar outcomes, which suggests a strengthening of these findings. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04438226 Show less
Baltussen, J.C.; Glas, N.A. de; Holstein, Y. van; Elst, M. van der; Trompet, S.; Boogaard, A.U. den; ... ; Portielje, J.E.A. 2023
Importance Although older patients are at increased risk of developing grade 3 or higher chemotherapy-related toxic effects, no studies, to our knowledge, have focused on the association between... Show moreImportance Although older patients are at increased risk of developing grade 3 or higher chemotherapy-related toxic effects, no studies, to our knowledge, have focused on the association between toxic effects and quality of life (QOL) and physical functioning.Objective To investigate the association between grade 3 or higher chemotherapy-related toxic effects and QOL and physical functioning over time in older patients.Design, Setting, and Participants In this prospective, multicenter cohort study, patients aged 70 years or older who were scheduled to receive chemotherapy with curative or palliative intent and a geriatric assessment were included. Patients were treated with chemotherapy between December 2015 and December 2021. Quality of life and physical functioning were analyzed at baseline and after 6 months and 12 months.Exposures Common Terminology Criteria for Adverse Events grade 3 or higher chemotherapy-related toxic effects.Main Outcomes and Measures The main outcome was a composite end point, defined as a decline in QOL and/or physical functioning or mortality at 6 months and 12 months after chemotherapy initiation. Associations between toxic effects and the composite end point were analyzed with multivariable logistic regression models.Results Of the 276 patients, the median age was 74 years (IQR, 72-77 years), 177 (64%) were male, 196 (71%) received chemotherapy with curative intent, and 157 (57%) had gastrointestinal cancers. Among the total patients, 145 (53%) had deficits in 2 or more of the 4 domains of the geriatric assessment and were classified as frail. Grade 3 or higher toxic effects were observed in 94 patients (65%) with frailty and 66 (50%) of those without frailty (P = .01). Decline in QOL and/or physical functioning or death was observed in 76% of patients with frailty and in 64% to 68% of those without frailty. Among patients with frailty, grade 3 or higher toxic effects were associated with the composite end point at 6 months (odds ratio [OR], 2.62; 95% CI, 1.14-6.05) but not at 12 months (OR, 1.09; 95% CI, 0.45-2.64) and were associated with mortality at 12 months (OR, 3.54; 95% CI, 1.50-8.33). Toxic effects were not associated with the composite end point in patients without frailty (6 months: OR, 0.76; 95% CI, 0.36-1.64; 12 months: OR, 1.06; 95% CI, 0.46-2.43).Conclusions and Relevance In this prospective cohort study of 276 patients aged 70 or older who were treated with chemotherapy, patients with frailty had more grade 3 or higher toxic effects than those without frailty, and the occurrence of toxic effects was associated with a decline in QOL and/or physical functioning or mortality after 1 year. Toxic effects were not associated with poor outcomes in patients without frailty. Pretreatment frailty screening and individualized treatment adaptions could prevent a treatment-related decline of remaining health. Show less
IMPORTANCE There are conflicting data on the association of antidrug antibodies with response tobiologic disease–modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA).OBJECTIVE To... Show moreIMPORTANCE There are conflicting data on the association of antidrug antibodies with response tobiologic disease–modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA).OBJECTIVE To analyze the association of antidrug antibodies with response to treatment for RA.DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed data from the ABI-RA (Anti-Biopharmaceutical Immunization: Prediction and Analysis of Clinical Relevance to Minimize the Riskof Immunization in Rheumatoid Arthritis Patients) multicentric, open, prospective study of patientswith RA from 27 recruiting centers in 4 European countries (France, Italy, the Netherlands, and theUK). Eligible patients were 18 years or older, had RA diagnosis, and were initiating a new bDMARD.Recruitment spanned from March 3, 2014, to June 21, 2016. The study was completed in June 2018,and data were analyzed in June 2022.EXPOSURES Patients were treated with a new bDMARD: adalimumab, infliximab (grouped as anti–tumor necrosis factor [TNF] monoclonal antibodies [mAbs]), etanercept, tocilizumab, and rituximabaccording to the choice of the treating physician.MAIN OUTCOMES AND MEASURES The primary outcome was the association of antidrug antibodypositivity with EULAR (European Alliance of Associations for Rheumatology; formerly, EuropeanLeague Against Rheumatism) response to treatment at month 12 assessed through univariate logisticregression. The secondary end points were the EULAR response at month 6 and at visits from month6 to months 15 to 18 using generalized estimating equation models. Detection of antidrug antibodyserum levels was performed at months 1, 3, 6, 12, and 15 to 18 using electrochemiluminescence (MesoScale Discovery) and drug concentration for anti-TNF mAbs, and etanercept in the serum wasmeasured using enzyme-linked immunosorbent assay.RESULTS Of the 254 patients recruited, 230 (mean [SD] age, 54.3 [13.7] years; 177 females [77.0%])were analyzed. At month 12, antidrug antibody positivity was 38.2% in patients who were treatedwith anti-TNF mAbs, 6.1% with etanercept, 50.0% with rituximab, and 20.0% with tocilizumab.There was an inverse association between antidrug antibody positivity (odds ratio [OR], 0.19; 95% CI,0.09-0.38; P < .001) directed against all biologic drugs and EULAR response at month 12. Analyzingall the visits starting at month 6 using generalized estimating equation models confirmed the inverseassociation between antidrug antibody positivity and EULAR response (OR, 0.35; 95% CI, 0.18-0.65;P < .001). A similar association was found for tocilizumab alone (OR, 0.18; 95% CI, 0.04-0.83;P = .03). In the multivariable analysis, antidrug antibodies, body mass index, and rheumatoid factorwere independently inversely associated with response to treatment. There was a significantly higher drug concentration of anti-TNF mAbs in patients with antidrug antibody–negative vs antidrugantibody–positive status (mean difference, −9.6 [95% CI, −12.4 to −6.9] mg/L; P < 001). Drugconcentrations of etanercept (mean difference, 0.70 [95% CI, 0.2-1.2] mg/L; P = .005) andadalimumab (mean difference, 1.8 [95% CI, 0.4-3.2] mg/L; P = .01) were lower in nonresponders vsresponders. Methotrexate comedication at baseline was inversely associated with antidrugantibodies (OR, 0.50; 95% CI, 0.25-1.00; P = .05).CONCLUSIONS AND RELEVANCE Results of this prospective cohort study suggest an associationbetween antidrug antibodies and nonresponse to bDMARDs in patients with RA. Monitoring antidrugantibodies could be considered in the treatment of these patients, particularly nonresponders tobiologic RA drugs. Show less
Importance Among patients with bipolar disorder, discordant findings have been published on the nephrotoxic effects of lithium therapy.Objective To quantify absolute and relative risks of chronic... Show moreImportance Among patients with bipolar disorder, discordant findings have been published on the nephrotoxic effects of lithium therapy.Objective To quantify absolute and relative risks of chronic kidney disease (CKD) progression and acute kidney injury (AKI) in people who initiated lithium compared with valproate therapy and to investigate the association between cumulative use and elevated lithium levels and kidney outcomes.Design, Setting, and Participants This cohort study had a new-user active-comparator design and used inverse probability of treatment weights to minimize confounding. Included patients initiated therapy with lithium or valproate from January 1, 2007, to December 31, 2018, and had a median follow-up of 4.5 years (IQR, 1.9-8.0 years). Data analysis began in September 2021, using routine health care data from the period 2006 to 2019 from the Stockholm Creatinine Measurements project, a recurrent health care use cohort of all adult residents in Stockholm, Sweden.Exposures New use of lithium vs new use of valproate and high (>1.0 mmol/L) vs low serum lithium levels.Main Outcomes and Measures Progression of CKD (composite of >30% decrease relative to baseline estimated glomerular filtration rate [eGFR] and kidney failure), AKI (by diagnosis or transient creatinine elevations), new albuminuria, and annual eGFR decrease. Outcomes by attained lithium levels were also compared in lithium users.Results The study included 10946 people (median [IQR] age, 45 [32-59] years; 6227 female [56.9%]), of whom 5308 initiated lithium therapy and 5638 valproate therapy. During follow-up, 421 CKD progression events and 770 AKI events were identified. Compared with patients who received valproate, those who received lithium did not have increased risk of CKD (hazard ratio [HR], 1.11 [95% CI, 0.86-1.45]) or AKI (HR, 0.88 [95% CI, 0.70-1.10]). Absolute 10-year CKD risks were low and similar: 8.4% in the lithium group and 8.2% in the valproate group. No difference in the risk of developing albuminuria or the annual rate of eGFR decrease was found between groups. Among more than 35000 routine lithium tests, only 3% of results were in the toxic range (>1.0 mmol/L). Lithium values greater than 1.0 mmol/L, compared with lithium values of 1.0 mmol/L or less, were associated with increased risk of CKD progression (HR, 2.86; 95% CI, 0.97-8.45) and AKI (HR, 3.51; 95% CI, 1.41-8.76).Conclusions and Relevance In this cohort study, compared with new use of valproate, new use of lithium was meaningfully associated with adverse kidney outcomes, with low absolute risks that did not differ between therapies. However, elevated serum lithium levels were associated with future kidney risks, particularly AKI, emphasizing the need for close monitoring and lithium dose adjustment. Show less
Heinen, F.J.; Arregle, F.; Brink, F.S. van den; Marsan, N.A.; Bernts, L.; Houthuizen, P.; ... ; Tanis, W. 2023
Importance It is suggested that patients with Cutibacterium acnes endocarditis often present without fever or abnormal inflammatory markers. However, no study has yet confirmed this statement.Obje...Show moreImportance It is suggested that patients with Cutibacterium acnes endocarditis often present without fever or abnormal inflammatory markers. However, no study has yet confirmed this statement.Objective To assess the clinical characteristics and outcomes of patients with C acnes endocarditis.Design, Setting, and Participants A case series of 105 patients presenting to 7 hospitals in the Netherlands and France (4 university hospitals and 3 teaching hospitals) with definite endocarditis according to the modified Duke criteria between January 1, 2010, and December 31, 2020, was performed. Clinical characteristics and outcomes were retrieved from medical records. Cases were identified by blood or valve and prosthesis cultures positive for C acnes, retrieved from the medical microbiology databases. Infected pacemaker or internal cardioverter defibrillator lead cases were excluded. Statistical analysis was performed in November 2022.Main Outcomes and Measures Main outcomes included symptoms at presentation, presence of prosthetic valve endocarditis, laboratory test results at presentation, time to positive results of blood cultures, 30-day and 1-year mortality rates, type of treatment (conservative or surgical), and endocarditis relapse rates.Results A total of 105 patients (mean [SD] age, 61.1 [13.9] years; 96 men [91.4%]; 93 patients [88.6%] with prosthetic valve endocarditis) were identified and included. Seventy patients (66.7%) did not experience fever prior to hospital admission, nor was it present at hospitalization. The median C-reactive protein level was 3.6 mg/dL (IQR, 1.2-7.5 mg/dL), and the median leukocyte count was 10.0 × 103/µL (IQR, 8.2-12.2 × 103/µL). The median time to positive blood culture results was 7 days (IQR, 6-9 days). Surgery or reoperation was indicated for 88 patients and performed for 80 patients. Not performing the indicated surgical procedure was associated with high mortality rates. Seventeen patients were treated conservatively, in accordance with the European Society of Cardiology guideline; these patients showed relatively high rates of endocarditis recurrence (5 of 17 [29.4%]).Conclusions and Relevance This case series suggests that C acnes endocarditis was seen predominantly among male patients with prosthetic heart valves. Diagnosing C acnes endocarditis is difficult due to its atypical presentation, with frequent absence of fever and inflammatory markers. The prolonged time to positivity of blood culture results further delays the diagnostic process. Not performing a surgical procedure when indicated seems to be associated with higher mortality rates. For prosthetic valve endocarditis with small vegetations, there should be a low threshold for surgery because this group seems prone to endocarditis recurrence. Show less
Popping, S.; Nichols, B.E.; Appelman, B.; Biemond, J.J.; Vergouwe, M.; Rosendaal, F.R.; ... ; Turn-Covid Study Grp 2023
IMPORTANCE Pre-exposure prophylaxis with neutralizing SARS-CoV-2 monoclonal antibodies (mAbs PrEP) prevents infection and reduces hospitalizations and the duration thereof for COVID-19 and death... Show moreIMPORTANCE Pre-exposure prophylaxis with neutralizing SARS-CoV-2 monoclonal antibodies (mAbs PrEP) prevents infection and reduces hospitalizations and the duration thereof for COVID-19 and death among high-risk individuals. However, reduced effectiveness due to a changing SARS-CoV-2 viral landscape and high drug prices remain substantial implementation barriers.OBJECTIVE To assess the cost-effectiveness of mAbs PrEP as COVID-19 PrEP.DESIGN, SETTING, AND PARTICIPANTS For this economic evaluation, a decision analytic model was developed and parameterized with health care outcome and utilization data from individuals with high risk for COVID-19. The SARS-CoV-2 infection probability, mAbs PrEP effectiveness, and drug pricing were varied. All costs were collected from a third-party payer perspective. Data were analyzed from September 2021 to December 2022.MAIN OUTCOMES AND MEASURES Health care outcomes including new SARS-CoV-2 infections, hospitalization, and deaths. The cost per death averted and cost-effectiveness ratios using a threshold for prevention interventions of $22000 or less per quality-adjusted life year (QALY) gained.RESULTS The clinical cohort consisted of 636 individuals with COVID-19 (mean [SD] age 63 [18] years; 341 [54%] male). Most individuals were at high risk for severe COVID-19, including 137 (21%) with a body mass index of 30 or higher, 60 (9.4%) with hematological malignant neoplasm, 108 (17%) post-transplantation, and 152 (23.9%) who used immunosuppressive medication before COVID-19. Within the context of a high (18%) SARS-CoV-2 infection probability and low (25%) effectiveness the model calculated a short-term reduction of 42% ward admissions, 31% intensive care unit (ICU) admissions, and 34% deaths. Cost-saving scenarios were obtained with drug prices of $275 and 75% or higher effectiveness. With a 100% effectiveness mAbs PrEP can reduce ward admissions by 70%, ICU admissions by 97%, and deaths by 92%. Drug prices, however, need to reduce to $550 for cost-effectiveness ratios less than $22000 per QALY gained per death averted and to $2200 for ratios between $22000 and $88000.CONCLUSIONS AND RELEVANCE In this study, use of mAbs PrEP for preventing SARS-CoV-2 infections was cost-saving at the beginning of an epidemic wave (high infection probability) with 75% or higher effectiveness and drug price of $275. These results are timely and relevant for decision-makers involved in mAbs PrEP implementation. When newer mAbs PrEP combinations become available, guidance on implementation should be formulated ensuring a fast rollout. Nevertheless, advocacy for mAbs PrEP use and critical discussion on drug prices are necessary to ensuring cost-effectiveness for different epidemic settings. Show less
ImportanceFractures of the hip have devastating effects on function and quality of life. Intramedullary nails (IMN) are the dominant implant choice for the treatment of trochanteric fractures of... Show moreImportanceFractures of the hip have devastating effects on function and quality of life. Intramedullary nails (IMN) are the dominant implant choice for the treatment of trochanteric fractures of the hip. Higher costs of IMNs and inconclusive benefit in comparison with sliding hip screws (SHSs) convey the need for definitive evidence.ObjectiveTo compare 1-year outcomes of patients with trochanteric fractures treated with the IMN vs an SHS. Design, Setting, and ParticipantsThis randomized clinical trial was conducted at 25 international sites across 12 countries. Participants included ambulatory patients aged 18 years and older with low-energy trochanteric (AO Foundation and Orthopaedic Trauma Association [AO/OTA] type 31-A1 or 31-A2) fractures. Patient recruitment occurred between January 2012 and January 2016, and patients were followed up for 52 weeks (primary end point). Follow-up was completed in January 2017. The analysis was performed in July 2018 and confirmed in January 2022. InterventionsSurgical fixation with a Gamma3 IMN or an SHS.Main Outcomes and MeasuresThe primary outcome was health-related quality of life (HRQOL), measured by the EuroQol-5 Dimension (EQ5D) at 1-year postsurgery. Secondary outcomes included revision surgical procedure, fracture healing, adverse events, patient mobility (measured by the Parker mobility score), and hip function (measured by the Harris hip score).ResultsIn this randomized clinical trial, 850 patients were randomized (mean [range] age, 78.5 [18-102] years; 549 [64.6% female) with trochanteric fractures to undergo fixation with either the IMN (n=423) or an SHS (n=427). A total of 621 patients completed follow-up at 1 year postsurgery (304 treated with the IMN [71.9%], 317 treated with an SHS [74.2%]). There were no significant differences between groups in EQ5D scores (mean difference, 0.02 points; 95% CI, -0.03 to 0.07 points; P=.42). Furthermore, after adjusting for relevant covariables, there were no between-group differences in EQ5D scores (regression coefficient, 0.00; 95% CI, -0.04 to 0.05; P=.81). There were no between-group differences for any secondary outcomes. There were also no significant interactions for fracture stability (beta [SE] , 0.01 [0.05]; P=.82) or previous fracture (beta [SE], 0.01 [0.10]; P=.88) and treatment group.Conclusions and RelevanceThis randomized clinical trial found that IMNs for the treatment of trochanteric fractures had similar 1-year outcomes compared with SHSs. These results suggest that the SHS is an acceptable lower-cost alternative for trochanteric fractures of the hip.Trial RegistrationClinicalTrials.gov Identifier: NCT01380444 Show less
IMPORTANCE The temporal trend in adverse events regarding stroke prevention for nonvalvular atrial fibrillation (NVAF) in the direct oral anticoagulant (DOAC) era was rarely investigated... Show moreIMPORTANCE The temporal trend in adverse events regarding stroke prevention for nonvalvular atrial fibrillation (NVAF) in the direct oral anticoagulant (DOAC) era was rarely investigated comprehensively, especially taking into account potential changes in patient characteristics and anticoagulation treatment.OBJECTIVE To investigate time trends in patient characteristics, anticoagulation treatment, and prognosis of patients with incident NVAF in the Netherlands.DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study assessed patients with incident NVAF initially recognized within a hospitalization between 2014 and 2018, using data from Statistics Netherlands. Participants were followed-up for 1 year from the hospital admission at which the incident NVAF diagnosis was made or until death, whichever occurred first. Data were analyzed from January 15, 2021, to March 8, 2023.EXPOSURE Calendar year of the incident NVAF diagnosis, according to which the participants were categorized into 5 cohorts.MAIN OUTCOMES AND MEASURES Outcomes of interest were baseline patient characteristics, anticoagulation treatment, and occurrence of ischemic stroke or major bleeding within the 1-year follow-up after incident NVAF.RESULTS Between 2014 and 2018, 301 301 patients (mean [SD] age, 74.2 [11.9] years; 169 748 [56.3%] male patients) experienced incident NVAF in the Netherlands, each of whom was categorized into 1 of 5 cohorts by calendar year. Baseline patient characteristics were broadly the same between cohorts with a mean (SD) CHA2DS2-VASc (congestive heart failure, hypertension, age >= 75 years [doubled], diabetes, stroke [doubled], vascular disease, age 65 to 74 years, and sex category [female]) score of 2.9 (1.7). The median (IQR) proportion of days covered by OACs (ie, vitamin K antagonists or DOACs) within the 1-year follow-up increased from 56.99% (0%-86.30%) to 75.62%(0%-94.52%), and DOACs increased from 5102 patients (13.5%) to 32 314 patients (72.0%) among those who received OACs, gradually replacing VKAs as the first choice of OACs. Over the course of the study, there were statistically significant decreases in the 1-year cumulative incidence of ischemic stroke (from 1.63%[95% CI, 1.52%-1.73%] to 1.39%[95% CI, 1.30%-1.48%) and major bleeding (from 2.50% [95% CI, 2.37%-2.63%] to 2.07%[95% CI, 1.96%-2.19%]), and the association was consistent after adjusting for baseline patient characteristics and excluding those with preexisting chronic anticoagulation.CONCLUSIONS AND RELEVANCE This cohort study of patients with incident NVAF diagnosed between 2014 and 2018 in the Netherlands found similar baseline characteristics, increased OAC use with DOACs being favored over time, and improved 1-year prognosis. Comorbidity burden, potential underuse of anticoagulation medications, and specific subgroups of patients with NVAF remain directions for future investigations and further improvement. Show less
IMPORTANCE Localization of subcentimeter ground glass opacities during minimally invasive thoracoscopic lung cancer resections is a significant challenge in thoracic oncology. Intraoperative... Show moreIMPORTANCE Localization of subcentimeter ground glass opacities during minimally invasive thoracoscopic lung cancer resections is a significant challenge in thoracic oncology. Intraoperative molecular imaging has emerged as a potential solution, but the availability of suitable fluorescence agents is a limiting factor.OBJECTIVE To evaluate the suitability of SGM-101, a carcinoembryonic antigen-related cell adhesion molecule type 5 (CEACAM5) receptor-targeted near-infrared fluorochrome, for molecular imagingguided lung cancer resections, because glycoprotein is expressed in more than 80% of adenocarcinomas.DESIGN, SETTING, AND PARTICIPANTS For this nonrandomized, proof-of-principal, phase 1 controlled trial, patients were divided into 2 groups between August 1, 2020, and January 31, 2022. Patients with known CEACAM5-positive gastrointestinal tumors suggestive of lung metastasis were selected as proof-of-principle positive controls. The investigative group included patients with lung nodules suggestive of primary lung malignant neoplasms. Patients 18 years or older without significant comorbidities that precluded surgical exploration with suspicious pulmonary nodules requiring surgical biopsy were included in the study.INTERVENTIONS SGM-101 (10mg) was infused up to 5 days before index operation, and pulmonary nodules were imaged using a near-infrared camera system with a dedicated thoracoscope.MAIN OUTCOMES AND MEASURES SGM-101 localization to pulmonary nodules and its correlation with CEACAM5 glycoprotein expression by the tumor as quantified by tumor and normal pulmonary parenchymal fluorescence.RESULTS Ten patients (5 per group; 5 male and 5 female; median [IQR] age, 66 [58-69] years) with 14 total lesions (median [range] lesion size, 0.91 [0.90-2.00] cm) were enrolled in the study. In the control group of 4 patients (1 patient did not undergo surgical resection because of abnormal preoperative cardiac clearance findings that were not deemed related to SGM-101 infusion), the mean (SD) lesion size was 1.33 (0.48) cm, 2 patients had elevated serum CEA markers, and 2 patients had normal serum CEA levels. Of the 4 patients who underwent surgical intervention, those with 2+ and 3+ tissue CEACAM5 expression had excellent tumor fluorescence, with a mean (SD) tumor to background ratio of 3.11 (0.45). In the patient cohort, the mean (SD) lesion size was 0.68 (0.22) cm, and no elevations in serum CEA levels were found. Lack of SGM-101 fluorescence was associated with benign lesions and with lack of CEACAM5 staining.CONCLUSIONS AND RELEVANCE This in-human proof-of-principle nonrandomized controlled trial demonstrated SGM-101 localization to CEACAM5-positive tumors with the detection of real-time near-infrared fluorescence in situ, ex vivo, and by immunofluorescence microscopy. These findings suggest that SGM-101 is a safe, receptor-specific, and feasible intraoperative molecular imaging fluorochrome that should be further evaluated in randomized clinical trials. Show less
IMPORTANCE There is a paucity of high-quality evidence about the long-term effects (ie, 3-5 years and beyond) of arthroscopic partial meniscectomy vs exercise-based physical therapy for patients... Show moreIMPORTANCE There is a paucity of high-quality evidence about the long-term effects (ie, 3-5 years and beyond) of arthroscopic partial meniscectomy vs exercise-based physical therapy for patients with degenerative meniscal tears. OBJECTIVES To compare the 5-year effectiveness of arthroscopic partial meniscectomy and exercise-based physical therapy on patient-reported knee function and progression of knee osteoarthritis in patients with a degenerative meniscal tear. Design, Setting, and Participants A noninferiority, multicenter randomized clinical trial was conducted in the orthopedic departments of 9 hospitals in the Netherlands. A total of 321 patients aged 45 to 70 years with a degenerative meniscal tear participated. Data collection took place between July 12, 2013, and December 4, 2020. INTERVENTIONS Patients were randomly allocated to arthroscopic partial meniscectomy or 16 sessions of exercise-based physical therapy. MAIN OUTCOMES AND MEASURES The primary outcome was patient-reported knee function (International Knee Documentation Committee Subjective Knee Form (range, 0 [worst] to 100 [best]) during 5 years of follow-up based on the intention-to-treat principle, with a noninferiority threshold of 11 points. The secondary outcome was progression in knee osteoarthritis shown on radiographic images in both treatment groups. RESULTS Of 321 patients (mean [SD] age, 58 [6.6] years; 161 women [50.2%]), 278 patients (87.1%) completed the 5-year follow-up with a mean follow-up time of 61.8 months (range, 58.8-69.5 months). From baseline to 5-year follow-up, the mean (SD) improvement was 29.6 (18.7) points in the surgery group and 25.1 (17.8) points in the physical therapy group. The crude between-group difference was 3.5 points (95% CI, 0.7-6.3 points; P < .001 for noninferiority). The 95% CI did not exceed the noninferiority threshold of 11 points. Comparable rates of progression of radiographic-demonstrated knee osteoarthritis were noted between both treatments. CONCLUSIONS AND RELEVANCE In this noninferiority randomized clinical trial after 5 years, exercise-based physical therapy remained noninferior to arthroscopic partial meniscectomy for patient-reported knee function. Physical therapy should therefore be the preferred treatment over surgery for degenerative meniscal tears. These results can assist in the development and updating of current guideline recommendations about treatment for patients with a degenerative meniscal tear. Show less
Dregmans, E.; Kaal, A.G.; Meziyerh, S.; Kolfschoten, N.E.; Aken, M.O. van; Schippers, E.F.; ... ; Nieuwkoop, C. van 2022
IMPORTANCE Misdiagnosis of infection is among the most commonly made diagnostic errors and is associated with increased morbidity and mortality. Little is known about how often misdiagnosed site of... Show moreIMPORTANCE Misdiagnosis of infection is among the most commonly made diagnostic errors and is associated with increased morbidity and mortality. Little is known about how often misdiagnosed site of infection occurs and its association with clinical outcomes.OBJECTIVES To evaluate the discrepancy between admission and discharge site of infection diagnoses among patients with suspected bacteremia, to explore factors associated with discrepant diagnoses, and to evaluate the association with clinical outcomes.DESIGN, SETTING, AND PARTICIPANTS This cohort study used electronic records of 1477 adult patients who were admitted to the hospital for suspected bacteremia from April 1, 2019, to May 31, 2020, and who had blood cultures taken at the emergency department at Haga Teaching Hospital, The Hague, the Netherlands. Suspected infection sites were classified into 8 categories at admission and discharge. Misdiagnosed site was defined as a discrepancy between the suspected site of infection at admission and at discharge.MAIN OUTCOMES AND MEASURES Clinical outcomes were 30-day mortality, intensive care unit admission, length of hospital stay, and antibiotic use, analyzed with logistic and linear regression. Risk factors for misdiagnosed site were determined using regression analysis.RESULTS A total of 1477 patients (820 [55.5%] male; median [IQR] age, 68 [56-78] years) were analyzed. The rate of misdiagnosed site of infection was 11.6% (171 of 1477); 3.1% of all patients (46 of 1477) ultimately had no infection. No association was found between misdiagnosis and 30-day mortality (adjusted odds ratio [aOR], 0.8; 95% CI, 03-1.9; P = .60), intensive care unit admission (aOR, 1.3; 95% CI, 0.6-3.0; P = .54), and hospital length of stay (adjusted increase of stay, 15.5%; 95% CI, -3.1% to 37.7%; P = .11). Misdiagnosed site was associated with receiving broad-spectrum antibiotics (aOR, 4.0; 95% CI, 1.8-8.8; P < .001). Older age, dementia, a positive urine sediment test result without urinary symptoms, and suspicion of an intravascular, central nervous system, or bone and joint infection were risk factors for misdiagnosed site of infection.CONCLUSIONS AND RELEVANCE In this cohort study, misdiagnosed site of infection occurred in 1 of 9 patients and was not associated with worse short-term clinical outcomes. Clinicians should be aware of risk factors associated with misdiagnosed site of infection and potential inappropriate antibiotic use. Show less
Ocak, G.; Boenink, R.; Noordzij, M.; Bos, W.J.W.; Vikse, B.E.; Cases, A.; ... ; Kramer, A. 2022
IMPORTANCE During the past decades, improvements in the prevention and management of myocardial infarction, stroke, and pulmonary embolism have led to a decline in cardiovascular mortality in the... Show moreIMPORTANCE During the past decades, improvements in the prevention and management of myocardial infarction, stroke, and pulmonary embolism have led to a decline in cardiovascular mortality in the general population. However, it is unknown whether patients receiving dialysis have also benefited from these improvements.OBJECTIVE To assess the mortality rates for myocardial infarction, stroke, and pulmonary embolism in a large cohort of European patients receiving dialysis compared with the general population.DESIGN, SETTING, AND PARTICIPANTS In this cohort study, adult patients who started dialysis between 1998 and 2015 from 11 European countries providing data to the European Renal Association Registry were and followed up for 3 years. Data were analyzed from September 2020 to February 2022.EXPOSURES Start of dialysis.MAIN OUTCOMES AND MEASURES The age- and sex-standardized mortality rate ratios (SMRs) with 95% CIs were calculated by dividing the mortality rates in patients receiving dialysis by the mortality rates in the general population for 3 equal periods (1998-2003, 2004-2009, and 2010-2015).RESULTS In total, 220 467 patients receiving dialysis were included in the study. Their median (IQR) age was 68.2 (56.5-76.4) years, and 82 068 patients (37.2%) were female. During follow-up, 83 912 patients died, of whom 7662 (9.1%) died because of myocardial infarction, 5030 (6.0%) died because of stroke, and 435 (0.5%) died because of pulmonary embolism. Between the periods 1998 to 2003 and 2010 to 2015, the SMR of myocardial infarction decreased from 8.1 (95% CI, 7.8-8.3) to 6.8 (95% CI, 6.5-7.1), the SMR of stroke decreased from 7.3 (95% CI, 7.0-7.6) to 5.8 (95% CI, 5.5-6.2), and the SMR of pulmonary embolism decreased from 8.7 (95% CI, 7.6-10.1) to 5.5 (95% CI, 4.5-6.6).CONCLUSIONS AND RELEVANCE In this cohort study of patients receiving dialysis, mortality rates for myocardial infarction, stroke, and pulmonary embolism decreased more over time than in the general population. Show less
IMPORTANCE Intra-articular (IA) glucocorticoid injection is widely used in patients with knee osteoarthritis (OA), but the safety of this technique is in question among physicians. Intramuscular ... Show moreIMPORTANCE Intra-articular (IA) glucocorticoid injection is widely used in patients with knee osteoarthritis (OA), but the safety of this technique is in question among physicians. Intramuscular (IM) glucocorticoid injection could be an alternative approach.OBJECTIVE To investigate whether an IM glucocorticoid injection is noninferior to an IA glucocorticoid injection in reducing knee pain for patients with knee OA in primary care.DESIGN, SETTING, AND PARTICIPANTS The KIS trial, a multicenter, open-label, randomized clinical noninferiority trial including patients with symptomatic knee OA, was conducted in 80 primary care general practices in the southwest of the Netherlands. The study was conducted from March 1, 2018, to July 28, 2020.INTERVENTIONS Patients were randomly allocated to receive an injection of triamcinolone acetonide, 40 mg, either IM in the ipsilateral ventrogluteal region or IA in the knee joint. All patients were followed up for 24 weeks.MAIN OUTCOMES AND MEASURES The pain score at 4 weeks measured with Knee Injury and Osteoarthritis Outcome Score (range, 0-100; 0 indicates extreme pain), with a noninferiority margin of -7 (IM minus IA). A per-protocol analysis was prespecified as the primary analysis.RESULTS A total of 145 patients (94 women [65%]; mean [SD] age, 67 [10] years) were included; of these, 138 patients (IM, 72; IA, 66) were included in the per-protocol analysis. Clinically relevant improvements in knee pain were reached up to 12 weeks after the injection in both groups. At 4 weeks, the estimated mean difference in the Knee Injury and Osteoarthritis Outcome Score between the 2 groups was -3.4 (95% CI, -10.1to 3.3). Noninferiority could not be declared because the lower limit exceeded the noninferiority margin. Intramuscular injection was noninferior to IA injection at 8 (mean difference, 0.7; 95% CI, -6.5 to 7.8) and 24 (mean difference, 1.6; 95% CI, -5.7 to 9.0) weeks. No significant difference was found among all the secondary outcomes. These results were similar for the sensitivity analysis in an intention-to-treat population. The most frequently reported adverse events were hot flush (IM, 7 [10%] vs IA, 14 [21%]) and headache (IM, 10 [14%] vs IA, 12 [18%]), and all events were classified as nonserious.CONCLUSIONS AND RELEVANCE Based on the findings of this trial, among patients with knee OA in primary care, IM glucocorticoid injection could present an inferior effect in reducing pain at 4 weeks compared with IA injection. Noninferiority of an IM injection was observed at 8 and 24 weeks after injection. This trial provides data for shared decision-making, taking into account the advantages and disadvantages of both types of injections. Show less
Wang, H.J.; Cushman, M.; Rosendaal, F.R.; Vlieg, A.V. 2022
IMPORTANCE Previous venous thrombosis (VT) is associated with risk of future VT, but quantification of risk over the life course is poorly understood. More information is needed for clinicians to... Show moreIMPORTANCE Previous venous thrombosis (VT) is associated with risk of future VT, but quantification of risk over the life course is poorly understood. More information is needed for clinicians to understand the association of remote history of VT with the risk of VT in older patients.OBJECTIVE To assess the association between a remote history of VT and the development of VT in older age.DESIGN, SETTING, AND PARTICIPANTS The Age and Thrombosis, Acquired and Genetic Risk Factors in the Elderly case-control study enrolled patients 70 years and older with VT and control individuals 70 years and older without VT between June 2008 and August 2011. The Age and Thrombosis, Acquired and Genetic Risk Factors in the Elderly study is a 2-center, population-based case-control study that was conducted in Burlington, Vermont, in the US and in Leiden, the Netherlands. Consecutively diagnosed patients with an objectively proven episode of VT (deep vein thrombosis of the leg or pulmonary embolism) were included. Control individualswere identified in the same geographic areas as the patients andwere randomly selected. Datawere analyzed between May 2021 and October 2021.EXPOSURES Self-reported remote VT (occurring >10 years before to enrollment).MAIN OUTCOMES AND MEASURES The main outcome was the risk of VT at older age. The association of self-reported history of remote VT with VT at older age was assessed by calculating odds ratios (ORs) as estimates of relative risk with 95% CIs.RESULTS A total of 460 patients with VT and 456 control participants were included. There were slightly more women than men in both groups (60.2% of patients [n = 277] were women and 52.4% of control participants [n = 239] were women), and the mean (range) age of patients was 78.7 (70.0-100.9) years, which was similar to the control participants. Compared with individuals without remote VT, those with a remote history of VT had an increased risk of VT (OR, 2.54; 95% CI, 1.56-4.13). The crude risk estimate was robust to adjustment and time since remote VT, that is, individuals with a VT 10 to 30 years ago (OR, 2.74; 95% CI, 1.34-5.57) and those with a VT more than 30 years ago (OR, 2.42; 95% CI, 1.21-4.84) had a an increased risk of VT. The populationattributable fraction of a remote history of VT was 7.7%.CONCLUSIONS AND RELEVANCE In this study, a remote history of VT was associated with risk of VT in older individuals. This quantification could assist clinicians in advising patients on VT prevention. Show less
Chung, J.E.R.E.W.; Geet, R. van; Helmond, N. van; Kastoer, C.; Bohringer, S.; Hout, W.B. van den; ... ; Blom, H.M. 2022
IMPORTANCE Carbon dioxide laser tonsillotomy performed under local anesthesia may be an effective and less invasive alternative than dissection tonsillectomy for treatment of tonsil-related... Show moreIMPORTANCE Carbon dioxide laser tonsillotomy performed under local anesthesia may be an effective and less invasive alternative than dissection tonsillectomy for treatment of tonsil-related afflictions.OBJECTIVE To compare functional recovery and symptom relief among adults undergoing tonsillectomy or tonsillotomy.DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial was conducted at 5 secondary and tertiary hospitals in the Netherlands from January 2018 to December 2019. Participants were 199 adult patients with an indication for surgical tonsil removal randomly assigned to either the tonsillectomy or tonsillotomy group.INTERVENTIONS For tonsillotomy, the crypts of the palatine tonsil were evaporated using a carbon dioxide laser under local anesthesia, whereas tonsillectomy consisted of total tonsil removal performed under general anesthesia.MAIN OUTCOMES AND MEASURES The primary outcome was time to functional recovery measured within 2 weeks after surgery assessed for a modified intention-to-treat population. Secondary outcomes were time to return to work after surgery, resolution of primary symptoms, severity of remaining symptoms, surgical complications, postoperative pain and analgesics use, and overall patient satisfaction assessed for the intention-to-treat population.RESULTS Of 199 patients (139 (70%] female; mean [SD] age, 29 [9] years), 98 were randomly assigned to tonsillotomy and 101v were randomly assigned to tonsillectomy. Recovery within 2 weeks after surgery was significantly shorter after tonsillotomy than after tonsillectomy (hazard ratio for recovery after tonsillectomy vs tonsillotomy, 0.3; 95% CI, 0.2-0.5). Two weeks after surgery, 72 (77%) patients in the tonsillotomy group were fully recovered compared with 26 (57%) patients in the tonsillectomy group. Time until return to work within 2 weeks was also shorter after tonsillotomy (median [IQR], 4.5 [3.0-7.0] days vs 12.0 [9.0-14.0] days; hazard ratio for return after tonsillectomy vs tonsillotomy, 0.3; 95% CI, 0.2-0.4.). Postoperative hemorrhage occurred in 2 patients (2%) in the tonsillotomy group and 8 patients (12%) in the tonsillectomy group. At 6 months after surgery, fewer patients in the tonsillectomy group (25; 35%) than in the tonsillotomy group (54; 57%) experienced persistent symptoms (difference of 22%; 95% CI, 7%-37%). Most patients with persistent symptoms in both the tonsillotomy (32 of 54; 59%) and tonsillectomy (16 of 25; 64%) groups reported mild symptoms 6 months after surgery.CONCLUSIONS AND RELEVANCE This randomized clinical trial found that compared with tonsillectomy performed under general anesthesia, laser tonsillotomy performed under local anesthesia had a significantly shorter and less painful recovery period. A higher percentage of patients had persistent symptoms after tonsillotomy, although the intensity of these symptoms was lower than before surgery. These results suggest that laser tonsillotomy performed under local anesthesia may be a feasible alternative to conventional tonsillectomy in this population. Show less
Brouwers, R.W.M.; Poort, E.K.J. van der; Kemps, H.M.C.; Akker-van Marle, M.E. van den; Kraal, J.J. 2021
IMPORTANCE Cardiac telerehabilitation (CTR) has been found to be a safe and beneficial alternative to traditional center-based cardiac rehabilitation (CR) and might be associated with higher... Show moreIMPORTANCE Cardiac telerehabilitation (CTR) has been found to be a safe and beneficial alternative to traditional center-based cardiac rehabilitation (CR) and might be associated with higher participation rates by reducing barriers to CR use. However, implementation of CTR interventions remains low, which may be owing to a lack of cost-effectiveness analyses of data from large-scale randomized clinical trials.OBJECTIVE To assess the cost-effectiveness of CTR with relapse prevention compared with centerbased CR among patients with coronary artery disease.DESIGN, SETTING, AND PARTICIPANTS This economic evaluation performed a cost-utility analysis of data from the SmartCare-CAD (Effects of Cardiac Telerehabilitation in Patients With Coronary Artery Disease Using a Personalized Patient-Centred ICT Platform) randomized clinical trial. The costeffectiveness and utility of 3 months of cardiac telerehabilitation followed by 9 months of relapse prevention were compared with the cost-effectiveness of traditional center-based cardiac rehabilitation. The analysis included 300 patients with stable coronary artery disease who received care at a CR center serving 2 general hospitals in the Netherlands between May 23, 2016, and July 26, 2018. All patients were entering phase 2 of outpatient CR and were followed up for 1 year (until August 14, 2019). Data were analyzed from September 21, 2020, to September 24, 2021.INTERVENTION After baseline measurements were obtained, participants were randomly assigned on a 1:1 ratio to receive CTR (intervention group) or center-based CR (control group) using computerized block randomization. After 6 supervised center-based training sessions, patients in the intervention group continued training at home using a heart rate monitor and accelerometer. Patients uploaded heart rate and physical activity data and discussed their progress during a weekly video consultation with their physical therapist. After 3 months, weekly coaching was concluded, and on-demand coaching was initiated for relapse prevention; patients were instructed to continue using their wearable sensors and were contacted in cases of nonadherence to the intervention or reduced exercise or physical activity volumes.MAIN OUTCOMES AND MEASURES Quality-adjusted life-years were assessed using the EuroQol 5-Dimension 5-Level survey (EQ-5D-5L) and the EuroQol Visual Analogue Scale (EQ-VAS), and cardiac-associated health care costs and non-health care costs were measured by health care consumption, productivity, and informal care questionnaires (the Medical Consumption Questionnaire, the Productivity Cost Questionnaire, and the Valuation of Informal Care Questionnaire) designed by the Institute for Medical Technology Assessment. Costs were converted to 2020 price levels (in euros) using the Dutch consumer price index (to convert to US dollars, euro values were multiplied by 1.142, which was the mean exchange rate in 2020).RESULTS Among 300 patients (266 men [88.7%]), the mean (SD) age was 60.7 (9.5) years. The quality of life among patients receiving CTR vs center-based CR was comparable during the study according to the results of both utility measures (mean difference on EQ-5D-5L: -0.004; P =.82; mean difference on EQ-VAS: -0.001; P =.92). Intervention costs were significantly higher for CTR (mean [SE], (sic)224 [(sic)4] [$256 ($4)]) compared with center-based CR (mean [SE], (sic)156 [(sic)5] [$178 ($6)]; P <.001); however, no difference in overall cardiac health care costs was observed between CTR (mean [SE], (sic)4787 [(sic)503] [$5467 ($574)] and center-based CR (mean [SE], (sic)5507 [(sic)659] [$6289 ($753)]; P =.36). From a societal perspective, CTR was associated with lower costs compared with center-based CR (mean [SE], (sic)20 495 [(sic)2751] [$23 405 ($3142)] vs (sic)24 381 [(sic)3613] [$27 843 ($4126)], respectively), although this difference was not statistically significant (-(sic)3887 [-$ 4439]; P =.34).CONCLUSIONS AND RELEVANCE In this economic evaluation, a CTR intervention with relapse prevention was likely to be cost-effective compared with center-based CR, suggesting that CTR maybe used as an alternative intervention for the treatment of patients with coronary artery disease. These results add to the evidence base in favor of CTR and may increase the implementation of CTR interventions in clinical practice. Show less
Wong, A.K.I.; Charpignon, M.; Kim, H.; Josef, C.; Hond, A.A.H. de; Fojas, J.J.; ... ; Celi, L.A. 2021
IMPORTANCE Discrepancies in oxygen saturation measured by pulse oximetry (Spo(2)), when compared with arterial oxygen saturation (Sao(2)) measured by arterial blood gas (ABG), may differentially... Show moreIMPORTANCE Discrepancies in oxygen saturation measured by pulse oximetry (Spo(2)), when compared with arterial oxygen saturation (Sao(2)) measured by arterial blood gas (ABG), may differentially affect patients according to race and ethnicity. However, the association of these disparities with health outcomes is unknown.OBJECTIVE To examine racial and ethnic discrepancies between Sao(2) and Spo(2) measures and their associations with clinical outcomes.DESIGN, SETTING, AND PARTICIPANTS This multicenter, retrospective, cross-sectional study included 3 publicly available electronic health record (EHR) databases (ie, the Electronic Intensive Care Unit-Clinical Research Database and Medical Information Mart for Intensive Care III and IV) as well as Emory Healthcare (2014-2021) and Grady Memorial (2014-2020) databases, spanning 215 hospitals and 382 ICUs. From 141 600 hospital encounters with recorded ABG measurements, 87 971 participants with first ABG measurements and an Spo(2) of at least 88% within 5 minutes before the ABG test were included.EXPOSURES Patients with hidden hypoxemia (ie, Spo(2) >= 88% but Sao(2) <88%).MAIN OUTCOMES AND MEASURES Outcomes, stratified by race and ethnicity, were Sao(2) for each Spo(2), hidden hypoxemia prevalence, initial demographic characteristics (age, sex), clinical outcomes (in-hospital mortality, length of stay), organ dysfunction by scores (Sequential Organ Failure Assessment [SOFA]), and laboratory values (lactate and creatinine levels) before and 24 hours after the ABG measurement.RESULTS The first Spo(2)-Sao(2) pairs from 87 971 patient encounters (27 713 [42.9%] women; mean [SE] age, 62.2 [17.0] years; 1919 [2.3%] Asian patients; 26 032 [29.6%] Black patients; 2397 [2.7%] Hispanic patients, and 57 632 [65.5%] White patients) were analyzed, with 4859 (5.5%) having hidden hypoxemia. Hidden hypoxemia was observed in all subgroups with varying incidence (Black: 1785 [6.8%]; Hispanic: 160 [6.0%]; Asian: 92 [4.8%]; White: 2822 [4.9%]) and was associated with greater organ dysfunction 24 hours after the ABG measurement, as evidenced by higher mean (SE) SOFA scores (7.2 [0.1] vs 6.29 [0.02]) and higher in-hospital mortality (eg, among Black patients: 369 [21.1%] vs 3557 [15.0%]; P < .001). Furthermore, patients with hidden hypoxemia had higher mean (SE) lactate levels before (3.15 [0.09] mg/dL vs 2.66 [0.02] mg/dL) and 24 hours after (2.83 [0.14] mg/dL vs 2.27 [0.02] mg/dL) the ABG test, with less lactate clearance (-0.54 [0.12] mg/dL vs -0.79 [0.03] mg/dL).CONCLUSIONS AND RELEVANCE In this study, there was greater variability in oxygen saturation levels for a given Spo(2) level in patients who self-identified as Black, followed by Hispanic, Asian, and White. Patients with and without hidden hypoxemia were demographically and clinically similar at baseline ABG measurement by SOFA scores, but those with hidden hypoxemia subsequently experienced higher organ dysfunction scores and higher in-hospital mortality. Show less
Kamath, C.C.; Giblon, R.; Kunneman, M.; Lee, A.I.; Branda, M.E.; Hargraves, I.G.; ... ; Shared Decision Ma 2021
IMPORTANCE How patients with atrial fibrillation (AF) and their clinicians consider cost in forming care plans remains unknown.OBJECTIVE To identify factors that inform conversations regarding... Show moreIMPORTANCE How patients with atrial fibrillation (AF) and their clinicians consider cost in forming care plans remains unknown.OBJECTIVE To identify factors that inform conversations regarding costs of anticoagulants for treatment of AF between patients and clinicians and outcomes associated with these conversations.DESIGN, SETTING, AND PARTICIPANTS This cohort study of recorded encounters and participant surveys at 5 US medical centers (including academic, community, and safety-net centers) from the SDM4AFib randomized trial compared standard AF care with and without use of a shared decisionmaking (SDM) tool. Included patients were considering anticoagulation treatment and were recruited by their clinicians between January 30, 2017, and June 27, 2019. Data were analyzed between August and November 2019.MAIN OUTCOMES AND MEASURES The incidence of and factors associated with cost conversations, and the association of cost conversations with patients' consideration of treatment cost burden and their choice of anticoagulation. RESULTS A total of 830 encounters (out of 922 enrolled participants) were recorded. Patients' mean (SD) age was 71.0 (10.4) years; 511 patients (61.6%) were men, 704 (86.0%) were White, 303 (40.9%) earned between $40 000 and $99 999 in annual income, and 657 (79.2%) were receiving anticoagulants. Clinicians' mean (SD) agewas 44.8 (13.2) years; 75 clinicians (53.2%) were men, and 111 (76%) practiced as physicians, with approximately half (69 [48.9%]) specializing in either internal medicine or cardiology. Cost conversations occurred in 639 encounters (77.0%) andwere more likely in the SDM arm (378 [90%] vs 261 [64%]; OR, 9.69; 95% CI, 5.77-16.29). In multivariable analysis, cost conversations were more likely to occur with female clinicians (66 [47%]; OR, 2.85; 95% CI, 1.216.71); consultants vs in-training clinicians (113 [75%]; OR, 4.0; 95% CI, 1.4-11.1); clinicians practicing family medicine (24 [16%]; OR, 12.12; 95% CI, 2.75-53.38]), internal medicine (35 [23%]; OR, 3.82; 95% CI, 1.25-11.70), or other clinicians (21 [14%]; OR, 4.90; 95% CI, 1.32-18.16) when compared with cardiologists; and for patients with an annual household income between $ 40 000 and $99 999 (249 [82.2%]; OR, 1.86; 95% CI, 1.05-3.29) compared with income below $ 40 000 or above $99 999. More patients who had cost conversations reported cost as a factor in their decision (244 [89.1%] vs 327 [69.0%]; OR 3.66; 95% CI, 2.43-5.50), but cost conversations were not associated with the choice of anticoagulation agent.CONCLUSIONS AND RELEVANCE Cost conversations were common, particularly for middle-income patients and with female and consultant-level primary care clinicians, aswell as in encounters using an SDM tool; they were associated with patients' consideration of treatment cost burden but not final treatment choice. With increasing costs of care passed on to patients, these findings can inform efforts to promote cost conversations in practice. Show less
Gerwen, M. van; Maggen, C.; Cardonick, E.; Verwaaijen, E.J.; Heuvel-eibrink, M. van den; Shmakov, R.G.; ... ; International Network Cancer Infer 2021
IMPORTANCE Chemotherapy during the first trimester of pregnancy should be avoided owing to the risk of congenital malformations. However, the precise gestational age at which chemotherapy can be... Show moreIMPORTANCE Chemotherapy during the first trimester of pregnancy should be avoided owing to the risk of congenital malformations. However, the precise gestational age at which chemotherapy can be initiated safely remains unclear.OBJECTIVE To assess congenital malformation rates associated with gestational age at initiation of chemotherapy among pregnant women with cancer.DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study evaluated all pregnant women who received chemotherapy between 1977 and 2019 registered in the International Network on Cancer, Infertility and Pregnancy (INCIP) database. Data were analyzed from February 15 to June 2, 2020.EXPOSURES Cancer treatment with chemotherapy during pregnancy.MAIN OUTCOMES AND MEASURES Analysis was focused on major and minor structural malformations in offspring, defined by EUROCAT, detected during pregnancy or at birth.RESULTS A total of 755 women in the INCIP database who underwent cancer treatment with chemotherapy during pregnancy were included in analysis. The median (range) age at cancer diagnosis was 33 (14-48) years. Among offspring, the major congenital malformation rate was 3.6% (95% CI, 2.4%-5.2%), and the minor congenital malformation rate was 1.9%(95% CI, 1.0%-3.1%). Chemotherapy exposure prior to 12 weeks gestational age was associated with a high rate of major congenital malformations, at 21.7%(95% CI, 7.5%-43.7%; odds ratio, 9.24 [95% CI, 3.13-27.30]). When chemotherapy was initiated after gestational age 12 weeks, the frequency of major congenital malformationswas 3.0%(95% CI, 1.9%-4.6%), whichwas similar to the expected rates in the general population. Minor malformations were comparable when exposure occurred before or after gestational age 12 weeks (4.3%[95% CI, 0.1%-21.9%] vs 1.8%[95% CI, 1.0-3.0]; odds ratio, 3.13 [95% CI, 0.39-25.28]). Of 29 women who received chemotherapy prior to 12 weeks gestation, 17 (58.6%) were not aware of pregnancy, and 6 (20.7%) experienced a miscarriage (3 women [10.3%]) or decided to terminate their pregnancy (3 women [10.3%]).CONCLUSIONS AND RELEVANCE This cohort study found that chemotherapy was associated with an increased risk of major congenital malformations only in the first 12 weeks of pregnancy. The risk of congenital malformations when chemotherapy was administered during the first trimester and the high number of incidental pregnancies during cancer treatment in the INCIP registry underscore the importance of contraceptive advice and pregnancy testing at the start of chemotherapeutic treatment in young women with cancer. Show less
Al-Wahsh, H.; Tangri, N.; Quinn, R.; Liu, P.; Ferguson, T.; Fiocco, M.; ... ; Ravani, P. 2021
IMPORTANCE Kidney failure risk prediction has implications for disease management, including advance care planning in adults with severe (ie, estimated glomerular filtration rate [eGFR] category 4,... Show moreIMPORTANCE Kidney failure risk prediction has implications for disease management, including advance care planning in adults with severe (ie, estimated glomerular filtration rate [eGFR] category 4, [G4]) chronic kidney disease (G4-CKD). Existing prediction tools do not account for the competing risk of death.OBJECTIVE To compare predictions of kidney failure (defined as estimated glomerular filtration rate [eGFR] <10 mL/min/1.73 m(2) or initiation of kidney replacement therapy) from models that do and do not account for the competing risk of death in adults with G4-CKD.DESIGN, SETTING, AND PARTICIPANTS This prognostic study linked population-based laboratory and administrative data (2002-2017) from 2 Canadian provinces (Alberta and Manitoba) to compare 3 kidney risk models: the standard Cox regression, cause-specific Cox regression, and Fine-Gray subdistribution hazard model. Participants were adults with incident G4-CKD (eGFR 15-29 mL/min/1.73 m(2)). Data analysis occurred between July and December 2020.MAIN OUTCOMES AND MEASURES The performance of kidney risk models at prespecified times and across categories of baseline characteristics, using calibration, reclassification, and discrimination (for competing risks). Predictive characteristics were age, sex, albuminuria, eGFR, diabetes, and cardiovascular disease.RESULTS The development and validation cohorts included 14 619 (7070 [48.4%] men; mean [SD] age, 74.1 [12.8] years) and 2295 (1152 [50.2] men; mean [SD] age, 71.9 [14.0] years) adults, respectively. The 3 models had comparable calibration up to 2 years from entry. Beyond 2 years, the standard Cox regression overestimated the risk of kidney failure. At 4 years, for example, risks predicted from standard Cox were 40% for people whose observed risks were less than 30%. At 2 years (risk cutoffs 10%-20%) and 5 years (risk cutoffs 15%-30%), 788 (5.4%) and 2162 (14.8%) people in the development cohort were correctly reclassified into lower- or higher-risk categories by the Fine-Gray model and incorrectly reclassified by standard Cox regression (the opposite was observed in 272 patients [1.9%] and 0 patients, respectively). In the validation cohort, 115 (5.0%) individuals and 389 (16.9%) individuals at 2 and 5 years, respectively, were correctly reclassified into lower- or higher-risk categories by the Fine-Gray model and incorrectly reclassified by the standard Cox regression; the opposite was observed in 98 (4.3%) individuals and 0 individuals, respectively. Differences in discrimination emerged at 4 to 5 years in the development cohort and at 1 to 2 years in the validation cohort (0.85 vs 0.86 and 0.78 vs 0.8, respectively). Performance differences were minimal during the entire follow-up in people at lower risk of death (ie, aged <= 65 years or without cardiovascular disease or diabetes) and greater in those with a higher risk of death. At 5 years, for example, in people aged 65 years or older, predicted risks from standard Cox were 50% where observed risks were less than 30%. Similar miscalibration was observed at 5 years in people with albuminuria greater than 30 mg/mmol, diabetes, or cardiovascular disease.CONCLUSIONS AND RELEVANCE In this study, predictions about the risk of kidney failure were minimally affected by consideration of competing risks during the first 2 years after developing G4-CKD. However, traditional methods increasingly overestimated the risk of kidney failure with longer follow-up time, especially among older patients and those with more comorbidity. Show less
