Category: Statistics

Clin Orthop Relat Res. 2024 Aug 14. doi: 10.1097/CORR.0000000000003193. Online ahead of print.

ABSTRACT

BACKGROUND: There is continuing debate about the ideal philosophy for component alignment in TKA. However, there are limited long-term functional and radiographic data on randomized comparisons of kinematic alignment versus mechanical alignment.

QUESTIONS/PURPOSES: We present the 10-year follow-up findings of a single-center, multisurgeon randomized controlled trial (RCT) comparing these two alignment philosophies in terms of the following questions: (1) Is there a difference in PROM scores? (2) Is there a difference in survivorship free from revision or reoperation for any cause? (3) Is there a difference in survivorship free from radiographic loosening?

METHODS: Ninety-nine patients undergoing primary TKA for osteoarthritis were randomized to either the mechanical alignment (n = 50) or kinematic alignment (n = 49) group. Eligibility for the study was patients undergoing unilateral TKA for osteoarthritis who were suitable for a cruciate-retaining TKA and could undergo MRI. Patients who had previous osteotomy, coronal alignment > 15° from neutral, a fixed flexion deformity > 15°, or instability whereby constrained components were being considered were excluded. Computer navigation was used in the mechanical alignment group, and patient-specific cutting blocks were used in the kinematic alignment group. At 10 years, 86% (43) of the patients in the mechanical alignment group and 80% (39) in the kinematic alignment group were available for follow-up performed as a per-protocol analysis. The PROMs that we assessed included the Knee Society Score, Oxford Knee Score, WOMAC, Forgotten Joint Score, and EuroQol 5-Dimension score. Kaplan-Meier analysis was used to assess survivorship free from reoperation (any reason) and revision (change or addition of any component). A single blinded observer assessed radiographs for signs of aseptic loosening (as defined by the presence of progressive radiolucent lines in two or more zones), which was reported as survivorship free from loosening.

RESULTS: At 10 years, there was no difference in any PROM score measured between the groups. Ten-year survivorship free from revision (components removed or added) likewise did not differ between the groups (96% [95% CI 91% to 99%] for the mechanical alignment group and 91% [95% CI 83% to 99%] for the kinematic alignment group; p = 0.38). There were two revisions in the mechanical alignment group (periprosthetic fracture, deep infection) and four in the kinematic alignment group (two secondary patella resurfacings, two deep infections). There was no statistically significant difference in reoperations for any cause between the two groups. There was no difference with regard to survivorship free from loosening on radiographic review (χ2 = 1.3; p = 0.52) (progressive radiolucent lines seen at 10 years were 0% for mechanical alignment and 3% for kinematic alignment).

CONCLUSION: Like the 2-year and 5-year outcomes previously reported, 10-year follow-up for this RCT demonstrated no functional or radiographic difference in outcomes between mechanical alignment and kinematic alignment TKA. Anticipated functional benefits of kinematic alignment were not demonstrated, and revision-free survivorship at 10 years did not differ between the two groups. Given the unknown long-term impact of kinematic alignment with regard to implant position (especially tibial component varus), we must conclude that mechanical alignment remains the reference standard for TKA. We could not demonstrate any advantage to kinematic alignment at 10-year follow-up.

LEVEL OF EVIDENCE: Level I, therapeutic study.

PMID:39145997 | DOI:10.1097/CORR.0000000000003193

JAMA Netw Open. 2024 Aug 1;7(8):e2427331. doi: 10.1001/jamanetworkopen.2024.27331.

NO ABSTRACT

PMID:39145983 | DOI:10.1001/jamanetworkopen.2024.27331

JAMA Netw Open. 2024 Aug 1;7(8):e2427350. doi: 10.1001/jamanetworkopen.2024.27350.

NO ABSTRACT

PMID:39145982 | DOI:10.1001/jamanetworkopen.2024.27350

JAMA Netw Open. 2024 Aug 1;7(8):e2428027. doi: 10.1001/jamanetworkopen.2024.28027.

NO ABSTRACT

PMID:39145981 | DOI:10.1001/jamanetworkopen.2024.28027

JAMA Netw Open. 2024 Aug 1;7(8):e2427786. doi: 10.1001/jamanetworkopen.2024.27786.

ABSTRACT

IMPORTANCE: Patients with trauma exhibit a complex balance of coagulopathy manifested by both bleeding and thrombosis. Antithrombin III is a plasma protein that functions as an important regulator of coagulation. Previous studies have found a high incidence of antithrombin III deficiency among patients with trauma.

OBJECTIVE: To assess whether changes in antithrombin III activity are associated with thrombohemorrhagic complications among patients with trauma.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted from December 2, 2015, to March 24, 2017, at a level I trauma center. A total of 292 patients with trauma were followed up from their arrival through 6 days from admission. Data, including quantification of antithrombin III activity, were collected for these patients. Thromboprophylaxis strategy; hemorrhage, deep vein thrombosis (DVT), and pulmonary embolism screenings; and follow-up evaluations were conducted per institutional protocols. Data analyses were performed from September 28, 2023, to June 4, 2024.

MAIN OUTCOMES AND MEASURES: The primary study outcome measurements were associations between antithrombin III levels and outcomes among patients with trauma, including ventilator-free days, hospital-free days, intensive care unit (ICU)-free days, hemorrhage, venous thromboembolic events, and mortality.

RESULTS: The 292 patients had a mean (SD) age of 54.4 (19.0) years and included 211 men (72.2%). Patients with an antithrombin III deficiency had fewer mean (SD) ventilator-free days (27.8 [5.1] vs 29.6 [1.4]; P = .0003), hospital-free days (20.3 [8.2] vs 24.0 [5.7]; P = 1.37 × 10-6), and ICU-free days (25.7 [4.9] vs 27.7 [2.3]; P = 9.38 × 10-6) compared with patients without a deficiency. Antithrombin III deficiency was also associated with greater rates of progressive intracranial hemorrhage (21.1% [28 of 133] vs 6.3% [10 of 159]; P = .0003) and thrombocytopenia (24.8% [33 of 133] vs 5.0% [8 of 159]; P = 1.94 × 10-6). Although antithrombin III deficiency was not significantly associated with DVT, patients who developed a DVT had a more precipitous decrease in antithrombin III levels that were significantly lower than patients who did not develop a DVT.

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with trauma, antithrombin III deficiency was associated with greater injury severity, increased hemorrhage, and increased mortality, as well as fewer ventilator-free, hospital-free, and ICU-free days. Although this was an associative study, these data suggest that antithrombin III levels may be useful in the risk assessment of patients with trauma.

PMID:39145978 | DOI:10.1001/jamanetworkopen.2024.27786

JAMA Netw Open. 2024 Aug 1;7(8):e2427956. doi: 10.1001/jamanetworkopen.2024.27956.

ABSTRACT

IMPORTANCE: Depression is common in adults experiencing homelessness. It is unclear whether continued homelessness is associated with more depressive symptoms.

OBJECTIVE: To examine the association between residential status and depressive symptoms in adults aged 50 years or older experiencing homelessness at study entry.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed results from the Health Outcomes of People Experiencing Homelessness in Older Middle Age (HOPE HOME) project, which in 2013 began enrolling adults aged 50 years or older experiencing homelessness in Oakland, California, and conducted structured interviews every 6 months for a mean duration of 5.5 years through 2023 (for this cohort study). Eligible participants included those aged 50 years or older, able to speak English, and experiencing homelessness at enrollment. We analyzed data collected from 2013 to 2023.

EXPOSURES: The exposure of interest was residential status. At follow-up visits, residential status was categorized as (1) homelessness (meeting the HEARTH [Homeless Emergency Assistance and Rapid Transition to Housing] Act definition) or (2) housed (living in a noninstitutional environment and not meeting the HEARTH Act definition).

MAIN OUTCOMES AND MEASURES: The primary outcome was moderate to severe depressive symptoms (with Center for Epidemiologic Studies-Depression [CES-D] scale score ≥22). The augmented inverse probability of treatment weighting (AIPTW) approach was used to examine the association between continued homelessness and depressive symptoms. The AIPTW adjusted for the following variables: number of chronic health conditions, age, sex, visiting a health care practitioner, receiving outpatient mental health treatment, receiving mental health medication, exposure to abuse, substance use disorder, and binge drinking.

RESULTS: The cohort was composed of 450 participants, of whom 343 (76.2%) were males, and the mean (SD) age was 58.5 (5.2) years. Participants completed a median (IQR) of 8.9 (8-11) follow-up visits. With 1640 person-years of observation time, participants continued homelessness for 880 person-years (57.1%) and experienced being housed for 715 person-years (44.3%). Many participants (304 [78.0%]) were housed during at least 1 follow-up visit. The odds of a CES-D scale score of 22 or higher was significantly higher among participants who continued experiencing homelessness than among housed participants (marginal causal odds ratio, 1.08; 95% CI, 1.04-1.11; P < .001).

CONCLUSIONS AND RELEVANCE: This cohort study found that continued homelessness was associated independently with increased odds of depressive symptoms. Obtaining housing may have a favorable role in depression and overall well-being of older adults experiencing homelessness and may be considered as a mental health intervention.

PMID:39145977 | DOI:10.1001/jamanetworkopen.2024.27956

JAMA Netw Open. 2024 Aug 1;7(8):e2428032. doi: 10.1001/jamanetworkopen.2024.28032.

ABSTRACT

IMPORTANCE: The characteristics and treatment strategies of atrial functional mitral regurgitation (AFMR) are poorly understood.

OBJECTIVE: To investigate the prevalence, clinical characteristics, and outcomes of mitral valve (MV) surgery in AFMR.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study, called the Real-World Observational Study for Investigating the Prevalence and Therapeutic Options for Atrial Functional Mitral Regurgitation (REVEAL-AFMR), was conducted across 26 Japanese centers (17 university hospitals, 1 national center, 3 public hospitals, and 5 private hospitals). All transthoracic echocardiography procedures performed from January 1 to December 31, 2019, were reviewed to enroll adult patients (aged ≥20 years) with moderate or severe AFMR, defined by preserved left ventricular function, a dilated left atrium, and an absence of degenerative valvular changes. Data were analyzed from May 8, 2023, to May 16, 2024.

EXPOSURES: Mitral valve surgery, with or without tricuspid valve intervention.

MAIN OUTCOMES AND MEASURES: The primary composite outcome included heart failure hospitalization and all-cause mortality.

RESULTS: In 177 235 patients who underwent echocardiography, 8867 had moderate or severe MR. Within this group, 1007 (11.4%) were diagnosed with AFMR (mean [SD] age, 77.8 [9.5] years; 55.7% female), of whom 807 (80.1%) had atrial fibrillation. Of these patients, 113 underwent MV surgery, with 92 (81.4%) receiving concurrent tricuspid valve surgery. Patients who underwent surgery were younger but had more severe MR (57.5% [n = 65] vs 9.4% [n = 84]; P < .001), a larger mean (SD) left atrial volume index (152.5 [97.8] mL/m2 vs 87.7 [53.1] mL/m2; P < .001), and a higher prevalence of heart failure (according to the New York Heart Association class III [marked limitation of physical activity] or class IV [symptoms of heart failure at rest], 26.5% [n = 30] vs 9.3% [n = 83]; P < .001) than those who remained under medical therapy. During a median follow-up of 1050 days (IQR, 741-1188 days), 286 patients (28.4%) experienced the primary outcome. Despite a more severe disease status, only the surgical group showed a decrease in natriuretic peptide levels at follow-up and had a significantly lower rate of the primary outcome (3-year event rates were 18.3% vs 33.3%; log-rank, P = .03). Statistical adjustments did not alter these findings.

CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that in patients with AFMR, who were typically older and predominantly had atrial fibrillation, MV surgery was associated with lower rates of adverse clinical outcomes. Future studies are warranted to investigate a possible causal relationship to better regulate cardiovascular medicine.

PMID:39145976 | DOI:10.1001/jamanetworkopen.2024.28032

JAMA Netw Open. 2024 Aug 1;7(8):e2428067. doi: 10.1001/jamanetworkopen.2024.28067.

ABSTRACT

IMPORTANCE: Small, geographically limited studies report that people with intellectual and developmental disabilities (IDD) have increased risk for serious pregnancy-related and birth-related challenges, including preeclampsia, preterm birth, and increased anxiety and depression, than their peers. United States-based population-level data among people with IDD are lacking.

OBJECTIVES: To identify perinatal and postpartum outcomes among a national, longitudinal sample of people with IDD enrolled in public health insurance, compare subgroups of people with IDD, and compare outcomes among people with IDD with those of peers without IDD.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used national Medicaid claims from January 1, 2008, to December 31, 2019, for 55 440 birthing people with IDD and a random sample of 438 557 birthing people without IDD. Medicaid funds almost half of all births and is the largest behavioral health insurer in the US, covering a robust array of services for people with IDD. Statistical analysis was performed from July 2023 to June 2024.

EXPOSURE: People who had a documented birth in Medicaid during the study years.

MAIN OUTCOME AND MEASURES: Perinatal outcomes were compared across groups using univariate and multivariate logistic regression. The probability of postpartum anxiety and depression was estimated using Kaplan-Meier and Cox proportional hazards regression.

RESULTS: The study sample included 55 440 birthing people with IDD (including 41 854 with intellectual disabilities [ID] and 13 586 with autism; mean [SD] age at first delivery, 24.9 [6.7] years) and a random sample of 438 557 birthing people without IDD (mean [SD] age at first delivery, 26.4 [6.3] years). People with IDD were younger at first observed delivery, had a lower prevalence of live births (66.6% vs 76.7%), and higher rates of obstetric conditions (gestational diabetes, 10.3% vs 9.9%; gestational hypertension, 8.7% vs 6.1%; preeclampsia, 6.1% vs 4.4%) and co-occurring physical conditions (heart failure, 1.4% vs 0.4%; hyperlipidemia, 5.3% vs 1.7%; ischemic heart disease, 1.5% vs 0.4%; obesity, 16.3% vs 7.4%) and mental health conditions (anxiety disorders, 27.9% vs 6.5%; depressive disorders, 32.1% vs 7.5%; posttraumatic stress disorder, 9.5% vs 1.2%) than people without IDD. The probability of postpartum anxiety (adjusted hazard ratio [AHR], 3.2 [95% CI, 2.9-3.4]) and postpartum depression (AHR, 2.4 [95% CI, 2.3-2.6]) was significantly higher among autistic people compared with people with ID only and people without IDD.

CONCLUSIONS AND RELEVANCE: In this retrospective cohort study, people with IDD had a younger mean age at first delivery, had lower prevalence of live births, and had poor obstetric, mental health, and medical outcomes compared with people without IDD, pointing toward a need for clinician training and timely delivery of maternal health care. Results highlight needed reproductive health education, increasing clinician knowledge, and expanding Medicaid to ensure access to care for people with IDD.

PMID:39145975 | DOI:10.1001/jamanetworkopen.2024.28067

JAMA Otolaryngol Head Neck Surg. 2024 Aug 15. doi: 10.1001/jamaoto.2024.2490. Online ahead of print.

ABSTRACT

IMPORTANCE: Oral and oropharyngeal cancer have low survival rates, and incidence continues to increase.

OBJECTIVE: To determine whether soluble CD44 and total protein (TP) are useful for monitoring head and neck cancer recurrence, either used in a point-of-care (POC) test or as individual laboratory-based biomarkers.

DESIGN, SETTING, AND PARTICIPANTS: This multi-institutional nonrandomized clinical trial testing a novel diagnostic/screening assay took place across the University of California, San Diego; Johns Hopkins University; the Greater Baltimore Medical Center; New York University; and the San Diego Veterans Affairs Hospital. Patients with newly biopsy-proven, untreated oral cavity and oropharyngeal cancer were enrolled. Patients were enrolled April 2017 to April 2019, and data were analyzed December 2022 to June 2023.

EXPOSURE: POC salivary oral rinse test.

MAIN OUTCOMES AND MEASURES: Oral rinses were collected at pretreatment baseline and 3, 6, 12, and 18 months after completion of therapy; participants were then followed up for 3 years to define disease status. Associations of baseline characteristics with a positive test were evaluated by Fisher exact test. The association of a positive value on the CD44 or TP test with progression-free survival was evaluated in an adjusted multivariable proportional hazards model.

RESULTS: Of 172 patients enrolled, the mean (SD) age was 62.5 (10.2) years, and 122 (70.9%) identified as male. Additionally, 92 patients (53.3%) had never smoked, 99 (57.6%) formerly or currently drank alcohol, and 113 (65.7%) presented with oropharyngeal cancers, which were positive for human papillomavirus in 95 (84.1%). Tumor site was associated with test results at baseline; patients with oral cavity cancer had a higher baseline positive POC test rate (47 of 51 [92.2%]) compared to patients with oropharyngeal cancer (85 of 110 [77.3%]). Using Cox regression models with CD44 or TP level as a time-varying covariate, a higher CD44 level showed a statistically significant association with a higher hazard of recurrence (hazard ratio, 1.06; 95% CI, 1.00-1.12), though the TP level was not statistically significant. In multivariate adjusted analysis, higher CD44 and TP levels were associated with increased hazard ratios of recurrence of 1.13 (95% CI, 1.04-1.22) and 3.51 (95% CI, 1.24-9.98), respectively.

CONCLUSION AND RELEVANCE: In this multi-institutional nonrandomized clinical trial of an assay, posttreatment longitudinal monitoring for elevated salivary CD44 and TP levels using an enzyme-linked immunosorbent assay-based laboratory test identified patients at increased risk of future cancer recurrence. The CD44 and TP rapid POC test holds some promise, but further development is needed for this indication.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03148665.

PMID:39145961 | DOI:10.1001/jamaoto.2024.2490

JAMA Oncol. 2024 Aug 15. doi: 10.1001/jamaoncol.2024.3044. Online ahead of print.

ABSTRACT

IMPORTANCE: Adjuvant ovarian function suppression (OFS) with oral endocrine therapy improves outcomes for premenopausal patients with hormone receptor-positive (HR+) breast cancer but adds adverse effects. A genomic biomarker for selecting patients most likely to benefit from OFS-based treatment is lacking.

OBJECTIVE: To assess the predictive and prognostic performance of the Breast Cancer Index (BCI) for OFS benefit in premenopausal women with HR+ breast cancer.

DESIGN, SETTING, AND PARTICIPANTS: This prospective-retrospective translational study used all available tumor tissue samples from female patients from the Suppression of Ovarian Function Trial (SOFT). These individuals were randomized to receive 5 years of adjuvant tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS. BCI testing was performed blinded to clinical data and outcome. The a priori hypothesis was that BCI HOXB13/IL17BR ratio (BCI[H/I])-high tumors would benefit more from OFS and high BCI portended poorer prognosis in this population. Settings spanned multiple centers internationally. Participants included premenopausal female patients with HR+ early breast cancer with specimens in the International Breast Cancer Study Group tumor repository available for RNA extraction. Data were collected from December 2003 to April 2021 and were analyzed from May 2022 to October 2022.

MAIN OUTCOMES AND MEASURES: Primary end points were breast cancer-free interval (BCFI) for the predictive analysis and distant recurrence-free interval (DRFI) for the prognostic analyses.

RESULTS: Tumor specimens were available for 1718 of the 3047 female patients in the SOFT intention-to-treat population. The 1687 patients (98.2%) who had specimens that yielded sufficient RNA for BCI testing represented the parent trial population. The median (IQR) follow-up time was 12 (10.5-13.4) years, and 512 patients (30.3%) were younger than 40 years. Tumors were BCI(H/I)-low for 972 patients (57.6%) and BCI(H/I)-high for 715 patients (42.4%). Patients with tumors classified as BCI(H/I)-low exhibited a 12-year absolute benefit in BCFI of 11.6% from exemestane plus OFS (hazard ratio [HR], 0.48 [95% CI, 0.33-0.71]) and an absolute benefit of 7.3% from tamoxifen plus OFS (HR, 0.69 [95% CI, 0.48-0.97]) relative to tamoxifen alone. In contrast, patients with BCI(H/I)-high tumors did not benefit from either exemestane plus OFS (absolute benefit, -0.4%; HR, 1.03 [95% CI, 0.70-1.53]; P for interaction = .006) or tamoxifen plus OFS (absolute benefit, -1.2%; HR, 1.05 [95% CI, 0.72-1.54]; P for interaction = .11) compared with tamoxifen alone. BCI continuous index was significantly prognostic in the N0 subgroup for DRFI (n = 1110; P = .004), with 12-year DRFI of 95.9%, 90.8%, and 86.3% in BCI low-risk, intermediate-risk, and high-risk N0 cancers, respectively.

CONCLUSIONS AND RELEVANCE: In this prospective-retrospective translational study of patients enrolled in SOFT, BCI was confirmed as prognostic in premenopausal women with HR+ breast cancer. The benefit from OFS-containing adjuvant endocrine therapy was greater for patients with BCI(H/I)-low tumors than BCI(H/I)-high tumors. BCI(H/I)-low status may identify premenopausal patients who are likely to benefit from this more intensive endocrine therapy.

PMID:39145953 | DOI:10.1001/jamaoncol.2024.3044