Tag: statistics

Bone Jt Open. 2023 Mar 14;4(3):168-181. doi: 10.1302/2633-1462.43.BJO-2022-0162.R1.

ABSTRACT

To develop prediction models using machine-learning (ML) algorithms for 90-day and one-year mortality prediction in femoral neck fracture (FNF) patients aged 50 years or older based on the Hip fracture Evaluation with Alternatives of Total Hip arthroplasty versus Hemiarthroplasty (HEALTH) and Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trials. This study included 2,388 patients from the HEALTH and FAITH trials, with 90-day and one-year mortality proportions of 3.0% (71/2,388) and 6.4% (153/2,388), respectively. The mean age was 75.9 years (SD 10.8) and 65.9% of patients (1,574/2,388) were female. The algorithms included patient and injury characteristics. Six algorithms were developed, internally validated and evaluated across discrimination (c-statistic; discriminative ability between those with risk of mortality and those without), calibration (observed outcome compared to the predicted probability), and the Brier score (composite of discrimination and calibration). The developed algorithms distinguished between patients at high and low risk for 90-day and one-year mortality. The penalized logistic regression algorithm had the best performance metrics for both 90-day (c-statistic 0.80, calibration slope 0.95, calibration intercept -0.06, and Brier score 0.039) and one-year (c-statistic 0.76, calibration slope 0.86, calibration intercept -0.20, and Brier score 0.074) mortality prediction in the hold-out set. Using high-quality data, the ML-based prediction models accurately predicted 90-day and one-year mortality in patients aged 50 years or older with a FNF. The final models must be externally validated to assess generalizability to other populations, and prospectively evaluated in the process of shared decision-making.

PMID:37051847 | DOI:10.1302/2633-1462.43.BJO-2022-0162.R1

Bone Jt Open. 2023 Mar 28;4(3):210-218. doi: 10.1302/2633-1462.43.BJO-2022-0153.R1.

ABSTRACT

To assess the incidence of radiological lateral osteoarthritis (OA) at 15 years after medial unicompartmental knee arthroplasty (UKA) and assess the relationship of lateral OA with symptoms and patient characteristics. Cemented Phase 3 medial Oxford UKA implanted by two surgeons since 1998 for the recommended indications were prospectively followed. A 15-year cumulative revision rate for lateral OA of 5% for this series was previously reported. A total of 163 unrevised knees with 15-year (SD 1) anterior-posterior knee radiographs were studied. Lateral joint space width (JSW_L) was measured and severity of lateral OA was classified as: nil/mild, moderate, and severe. Preoperative and 15-year Oxford Knee Scores (OKS) and American Knee Society Scores were determined. The effect of age, sex, BMI, and intraoperative findings was analyzed. Statistical analysis included one-way analysis of variance and Kruskal-Wallis H test, with significance set at 5%. The mean age was 80.6 years (SD 8.3), with 84 females and 79 males. The mean JSW_L was 5.6 mm (SD 1.4), and was not significantly related to age, sex, or intraoperative findings. Those with BMI > 40 kg/m² had a smaller JSW_L than those with a ‘normal’ BMI (p = 0.039). The incidence of severe and moderate lateral OA were both 4.9%. Overall, 2/142 (1.4%) of those with nil/mild lateral OA, 1/8 (13%) with moderate, and 2/8 (25%) with severe subsequently had a revision. Those with severe (mean OKS 35.6 (SD 9.3)) and moderate OA (mean OKS 35.8 (SD 10.5)) tended to have worse outcome scores than those with nil/mild (mean OKS 39.5 (SD 9.2)) but the difference was only significant for OKS-Function (p = 0.044). This study showed that the rate of having severe or moderate radiological lateral OA at 15 years after medial UKA was low (both 4.9%). Although patients with severe or moderate lateral OA had a lower OKS than those with nil/mild OA, their mean scores (OKS 36) would be classified as good.

PMID:37051833 | DOI:10.1302/2633-1462.43.BJO-2022-0153.R1

Bone Joint Res. 2023 Mar 9;12(3):212-218. doi: 10.1302/2046-3758.123.BJR-2022-0312.R1.

ABSTRACT

Glucose-insulin-potassium (GIK) is protective following cardiac myocyte ischaemia-reperfusion (IR) injury, however the role of GIK in protecting skeletal muscle from IR injury has not been evaluated. Given the similar mechanisms by which cardiac and skeletal muscle sustain an IR injury, we hypothesized that GIK would similarly protect skeletal muscle viability. A total of 20 C57BL/6 male mice (10 control, 10 GIK) sustained a hindlimb IR injury using a 2.5-hour rubber band tourniquet. Immediately prior to tourniquet placement, a subcutaneous osmotic pump was placed which infused control mice with saline (0.9% sodium chloride) and treated mice with GIK (40% glucose, 50 U/l insulin, 80 mEq/L KCl, pH 4.5) at a rate of 16 µl/hr for 26.5 hours. At 24 hours following tourniquet removal, bilateral (tourniqueted and non-tourniqueted) gastrocnemius muscles were triphenyltetrazolium chloride (TTC)-stained to quantify percentage muscle viability. Bilateral peroneal muscles were used for gene expression analysis, serum creatinine and creatine kinase activity were measured, and a validated murine ethogram was used to quantify pain before euthanasia. GIK treatment resulted in a significant protection of skeletal muscle with increased viability (GIK 22.07% (SD 15.48%)) compared to saline control (control 3.14% (SD 3.29%)) (p = 0.005). Additionally, GIK led to a statistically significant reduction in gene expression markers of cell death (CASP3, p < 0.001) and inflammation (NOS2, p < 0.001; IGF1, p = 0.007; IL-1β, p = 0.002; TNFα, p = 0.012), and a significant reduction in serum creatine kinase (p = 0.004) and creatinine (p < 0.001). GIK led to a significant reduction in IR-related pain (p = 0.030). Systemic GIK infusion during and after limb ischaemia protects murine skeletal muscle from cell death, kidneys from reperfusion metabolites, and reduces pain by reducing post-ischaemic inflammation.

PMID:37051831 | DOI:10.1302/2046-3758.123.BJR-2022-0312.R1

Bone Jt Open. 2023 Mar 14;4(3):182-187. doi: 10.1302/2633-1462.43.BJO-2023-0003.R1.

ABSTRACT

Hip resurfacing remains a potentially valuable surgical procedure for appropriately-selected patients with optimised implant choices. However, concern regarding high early failure rates continues to undermine confidence in use. A large contributor to failure is adverse local tissue reactions around metal-on-metal (MoM) bearing surfaces. Such phenomena have been well-explored around MoM total hip arthroplasties, but comparable data in equivalent hip resurfacing procedures is lacking. In order to define genetic predisposition, we performed a case-control study investigating the role of human leucocyte antigen (HLA) genotype in the development of pseudotumours around MoM hip resurfacings. A matched case-control study was performed using the prospectively-collected database at the host institution. In all, 16 MoM hip resurfacing ‘cases’ were identified as having symptomatic periprosthetic pseudotumours on preoperative metal artefact reduction sequence (MARS) MRI, and were subsequently histologically confirmed as high-grade aseptic lymphocyte-dominated vasculitis-associated lesions (ALVALs) at revision surgery. ‘Controls’ were matched by implant type in the absence of evidence of pseudotumour. Blood samples from all cases and controls were collected prospectively for high resolution genetic a nalysis targeting 11 separate HLA loci. Statistical significance was set at 0.10 a priori to determine the association between HLA genotype and pseudotumour formation, given the small sample size. Using a previously-reported ALVAL classification, the majority of pseudotumour-positive caseswere found to have intermediate-grade group 2 (n = 10; 63%) or group 3 (n = 4; 25%) histological findings. Two further patients (13%) had high-grade group 4 lesions. HLA-DQB1*05:03:01 (p = 0.0676) and HLA-DRB1*14:54:01 (p = 0.0676) alleles were significantly associated with a higher risk of pseudotumour formation, while HLA-DQA1*03:01:01 (p = 0.0240), HLA-DRB1*04:04:01 (p = 0.0453), HLA-C*01:02:01 (p = 0.0453), and HLA-B*27:05:02 (p = 0.0855) were noted to confer risk reduction. These findings confirm the association between specific HLA genotypes and the risk of pseudotumour development around MoM hip resurfacings. Specifically, the two ‘at risk’ alleles (DQB1*05:03:01 and DRB1*14:54:01) may hold clinical value in preoperative screening and prospective surgical decision-making.

PMID:37051827 | DOI:10.1302/2633-1462.43.BJO-2023-0003.R1

Bone Jt Open. 2023 Mar 16;4(3):198-204. doi: 10.1302/2633-1462.43.BJO-2023-0006.R1.

ABSTRACT

Cementing in arthroplasty for hip fracture is associated with improved postoperative function, but may have an increased risk of early mortality compared to uncemented fixation. Quantifying this mortality risk is important in providing safe patient care. This study investigated the association between cement use in arthroplasty and mortality at 30 days and one year in patients aged 50 years and over with hip fracture. This retrospective cohort study used linked data from the Australian Hip Fracture Registry and the National Death Index. Descriptive analysis and Kaplan-Meier survival curves tested the unadjusted association of mortality between cemented and uncemented procedures. Multilevel logistic regression, adjusted for covariates, tested the association between cement use and 30-day mortality following arthroplasty. Given the known institutional variation in preference for cemented fixation, an instrumental variable analysis was also performed to minimize the effect of unknown confounders. Adjusted Cox modelling analyzed the association between cement use and mortality at 30 days and one year following surgery. The 30-day mortality was 6.9% for cemented and 4.9% for uncemented groups (p = 0.003). Cement use was significantly associated with 30-day mortality in the Kaplan-Meier survival curve (p = 0.003). After adjusting for covariates, no significant association between cement use and 30-day mortality was shown in the adjusted multilevel logistic regression (odd rati0 (OR) 1.1, 95% confidence interval (CI) 0.9 to 1.5; p = 0.366), or in the instrumental variable analysis (OR 1.0, 95% CI 0.9 to 1.0, p=0.524). There was no significant between-group difference in mortality within 30days (hazard ratio (HR) 0.9, 95% CI 0.7to 1.1; p = 0.355) or one year (HR 0.9 95% CI 0.8 to 1.1; p = 0.328) in the Cox modelling. No statistically significant difference in patient mortality with cement use in arthroplasty was demonstrated in this population, once adjusted for covariates. This study concludes that cementing in arthroplasty for hip fracture is a safe means of surgical fixation.

PMID:37051818 | DOI:10.1302/2633-1462.43.BJO-2023-0006.R1

Bone Joint Res. 2023 Apr 1;12(4):231-244. doi: 10.1302/2046-3758.124.BJR-2022-0335.R1.

ABSTRACT

Spinopelvic characteristics influence the hip’s biomechanical behaviour. However, to date there is little knowledge defining what ‘normal’ spinopelvic characteristics are. This study aims to determine how static spinopelvic characteristics change with age and ethnicity among asymptomatic, healthy individuals. This systematic review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to identify English studies, including ≥ 18-year-old participants, without evidence of hip or spine pathology or a history of previous surgery or interventional treatment, documenting lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI). From a total of 2,543 articles retrieved after the initial database search, 61 articles were eventually selected for data extraction. When all ethnicities were combined the mean values for LL, SS, PT, and PI were: 47.4° (SD 11.0°), 35.8° (SD 7.8°), 14.0° (SD 7.2°), and 48.8° (SD 10°), respectively. LL, SS, and PT had statistically significant (p < 0.001) changes per decade at: -1.5° (SD 0.3°), -1.3° (SD 0.3°), and 1.4° (SD 0.1°). Asian populations had the largest age-dependent change in LL, SS, and PT compared to any other ethnicity per decade at: -1.3° (SD 0.3°) to -0.5° (SD 1.3°), -1.2° (SD 0.2°) to -0.3° (SD 0.3°), and 1.7° (SD 0.2°) versus 1.1° (SD 0.1°), respectively. Ageing alters the orientation between the spine and pelvis, causing LL, SS, and PT to modify their orientations in a compensatory mechanism to maintain sagittal alignment for balance when standing. Asian populations have the largest degree of age-dependent change to their spinopelvic parameters compared to any other ethnicity, likely due to their lower PI.

PMID:37051815 | DOI:10.1302/2046-3758.124.BJR-2022-0335.R1

Diabetes Obes Metab. 2023 Apr 12. doi: 10.1111/dom.15093. Online ahead of print.

ABSTRACT

AIM: This meta-analysis was performed to assess the efficacy and safety of multifactorial intensive treatment (MT) in patients with diabetic kidney disease (DKD).

METHODS: We systematically searched PubMed, Embase and Web of science from their inception to February 2023 to identify randomized control trials (RCTs) evaluating the effect and safety of MT in patients with DKD. The quality of included RCTs was assessed using the risk of bias tool. The outcomes were expressed as hazard ratios (HR), risk ratio (RR) or weight mean difference (WMD) with 95% confidence intervals (95% CI), with a meta-analysis of a fixed-effect or random-effect model.

RESULTS: Five RCTs were included for data analysis. The pooled analysis showed that, MT was associated with significant reductions in all-cause mortality (HR=0.75, 95%CI: 0.60, 0.93; P=0.008) and cardiovascular event disease (CVD) rate (HR=0.55, 95%CI: 0.44, 0.68; P<0.001). MT significantly decreased the retinopathy progression (HR=0.79, 95%CI: 0.66, 0.95; P=0.011), progression of macroalbuminuria (HR=0.64, 95%CI: 0.43, 0.95; P=0.027) and progression of microalbuminuria (HR=0.69, 95%CI: 0.56, 0.86; P=0.001). In addition, MT was not associated with an increased risk of all adverse events (RR=1.00, 95%CI: 0.97, 1.03; P=0.830) and all severe adverse events (RR=0.92, 95%CI: 0.74, 1.15; P=0.478), and the statistical power was confirmed by trial sequential analysis.

CONCLUSION: The present study suggested that MT had a remarkable benefit on the risk of all-cause mortality and CVD in patients with DKD. Our results were promising, but had certain limitations, which warrants additional large-scale RCTs to validate our findings. This article is protected by copyright. All rights reserved.

PMID:37046362 | DOI:10.1111/dom.15093

Breast Cancer Res. 2023 Apr 12;25(1):39. doi: 10.1186/s13058-023-01626-3.

ABSTRACT

PURPOSE: Ki67 assessed at diagnosis (Ki67_baseline) is an important prognostic factor in primary oestrogen receptor-positive (ER +) breast cancer. Proportional change in Ki67 after 2 weeks (∆Ki67_2week) is associated with clinical benefit from endocrine therapies and residual Ki67 (Ki67_2week) with recurrence-free survival. The aim was to define the association between Ki67_baseline and after aromatase inhibitor (AI) exposure ∆Ki67_2week and Ki67_2week with key prognostic and biologic factors utilising data from the POETIC study.

PATIENTS AND METHODS: In POETIC 4480 postmenopausal patients with primary ER and/or PgR + breast cancer were randomised 2:1 to 2 weeks’ presurgical AI (anastrozole or letrozole) or no presurgical treatment (control). Ki67 was measured centrally in core-cut biopsies taken prior to AI and in core-cuts or the excision biopsy at surgery. Relationships between the Ki67 and biologic factors were explored using linear regression.

RESULTS: Established associations of Ki67_baseline with biologic factors including PgR status, tumour grade, tumour size, histological subtype, nodal status, and vascular invasion were confirmed in the HER2- subpopulation. In the HER2 + subpopulation only grade and tumour size were significantly associated with Ki67_baseline. In control group Ki67_2week was 18% lower than Ki67_baseline (p < 0.001) when Ki67_2week was measured in excision biopsies but not when measured in core-cuts. Median suppression by AIs (∆Ki67_2week) was 79.3% (IQR: -89.9 to -54.6) and 53.7% (IQR: -78.9 to -21.1) for HER2-negative and HER2-positive cases, respectively. Significantly less suppression occurred in PgR- vs PgR + and HER2 + vs HER2- tumours which remained apparent after adjustment for 2-week sample type.

CONCLUSIONS: The magnitude of this study allowed characterisation of relationships between Ki67_baseline, ∆Ki67_2week and Ki67_2week with high degrees of confidence providing a reference source for other studies. Lower values of Ki67 occur when measured on excision biopsies and could lead to apparent but artefactual decreases in Ki67: this should be considered when either ∆Ki67_2week or Ki67_2week is used in routine clinical practice to aid treatment decisions or in clinical trials assessing new drug therapies.

PMID:37046348 | DOI:10.1186/s13058-023-01626-3

Int J Retina Vitreous. 2023 Apr 12;9(1):27. doi: 10.1186/s40942-023-00456-x.

ABSTRACT

BACKGROUND: We investigated the effect of the number of laser shots applied on the myopic variables to elucidate the mechanism of myopia development in laser-treated retinopathy of prematurity (ROP) eyes.

METHODS: A total of 33 eyes of 17 infants with ROP who underwent laser treatment were included in the analysis. Cycloplegic retinoscopic refraction testing was carried out and the spherical equivalent (SE) was calculated. Relationships between SE and various variables (including the number of laser shots applied) were examined. In addition, an age-matched control group without ROP was prepared and ocular structural parameters were compared.

RESULTS: Although there was no statistical difference in axial length (AL) between two groups (p = 0.88), SE was significantly more myopic in the ROP group (p < 0.001). SE was associated with AL, corneal refraction (CR), and crystalline lens power (CLP) in the ROP group. Of these three factors (AL, CR, and CLP), CLP and the number of laser shots applied were significantly correlated (p = 0.003); however, no correlations were observed between the number of laser shots and AL or CR (p = 0.15 and 0.10, respectively). Very similar tendency was observed in the analysis of the difference between right and left eyes in each child.

CONCLUSIONS: In laser-treated ROP eyes, AL, CR, and CLP were related to the degree of myopia. Moreover, the number of shots applied also affected the myopic status in laser-treated ROP eyes. Among AL, CR, and CLP, only CLP was correlated with the laser shots applied.

PMID:37046346 | DOI:10.1186/s40942-023-00456-x

World J Surg Oncol. 2023 Apr 12;21(1):130. doi: 10.1186/s12957-023-03011-y.

ABSTRACT

BACKGROUND: We aimed to investigate the different metastases and prognoses of neuroblastoma (NB) and determine the risk factors of metastasis.

METHOD: Data of 1224 patients with NB were obtained from the Surveillance, Epidemiology and End Results database (2010-2018). Pearson’s chi-square test, Kaplan-Meier analysis, multivariable logistic regression and Cox regression analysis were used to determine the factors associated with prognosis.

RESULTS: The overall incidence of NB was an age-adjusted rate of 8.2 patients per 1,000,000 children. In total, 1224 patients were included in our study, with 599 patients (48.9%) exhibiting distant metastases. Compared to patients with non-metastatic NB, a greater proportion of patients with metastatic NB were under 1 year, male, had an adrenal primary site, unilateral tumour, a tumour size > 10 cm, neuroblastoma-not otherwise specified (NB-NOS), second malignant neoplasms and were more likely to choose radiotherapy and chemotherapy. Multivariate Cox regression showed that metastasis was an independent risk factor for overall survival (OS) and cancer-specific survival (CSS). The survival rate of non-metastatic patients with NB was better than those with metastasis (OS: hazard ratio (HR): 0.248, P < 0.001; CSS: HR: 0.267, P < 0.001). The bone and liver were the two most common isolated metastatic sites in NB. However, no statistical difference was observed in OS and CSS between the only bone metastasis group, only liver metastasis group and bone metastasis combined with liver metastasis group (all P > 0.05). Additionally, age at diagnosis > 1 year (odds ratio (OR): 3.295, P < 0 .001), grades III-IV (OR: 26.228, P < 0 .001) and 5-10 cm tumours (OR: 1.781, P < 0 .001) increased the risk of bone metastasis of NB. Moreover, no surgical treatment (OR: 2.441, P < 0 .001) increased the risk of liver metastasis of NB.

CONCLUSION: Metastatic NB has unique clinicopathological features, with the bone and liver as the most common single metastatic sites of NB. Therefore, more aggressive treatment is recommended for high-risk children with NB displaying distant metastases.

PMID:37046344 | DOI:10.1186/s12957-023-03011-y