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Patients with idiopathic fibrosing interstitial pneumonias (f-IIPs) mainly suffer from dyspnea. Refractory dyspnea, defined as persistent dyspnea despite optimal treatment, could be the signal to prescribe dyspnea relievers. We aimed to examine the prevalence and characteristics of refractory dyspnea in consecutive patients with f-IIPs. Refractory dyspnea was defined by an mMRC≥3 and also by a VAS dyspnea score≥2 at rest. The sensory and affective characteristics of refractory dyspnea (mMRC≥3) and associated quality of life (QoL) anxiety and depression were compared with non-refractory dyspnea (mMRC1-2) using the Multidimensional Dyspnea Profile (MDP), King's Brief Interstitial Lung Disease (KBILD) and Hospital Anxiety and Depression scale (HADs). We included 40 patients (24 men), aged 72 [68-79], FVC of 71 % [59-86] and DLCO 47 % [40-49]. Refractory dyspnea, was found in 38 % (95%CI:23-54) when defined by mMRC≥3 and in 67 % (95%CI:50-81) using a resting VAS dyspnea score ≥2. The agreement between the two definitions was low. Patients with refractory dyspnea (mMRC≥3) were more often women (60 % vs.28 %, p = 0.046), had a lower DLCO (24 % [22-43] vs.47 % [43-51], p = 0.014) and more frequently used oxygen (60 % vs.12 %, p = 0.003); they experience more intense air hunger (5/10 [3-6] vs.2/10 [0-5], p = 0.018)). No significant differences were observed in VAS, MDP, KBILD, or HADs scores between refractory and non-refractory dyspnea patients. Our results indicate a significant frequency of refractory dyspnea in patients with f-IIPs and an association with air hunger but no impact on the affective dimension of dyspnea, anxiety, depression and QoL, suggesting that the mMRC score might not accurately identify patients distressed by their breathlessness.
Subject(s)
Idiopathic Interstitial Pneumonias , Lung Diseases, Interstitial , Male , Humans , Female , Quality of Life , Idiopathic Interstitial Pneumonias/complications , Idiopathic Interstitial Pneumonias/epidemiology , Lung Diseases, Interstitial/complications , Lung Diseases, Interstitial/epidemiology , Dyspnea/diagnosis , Dyspnea/epidemiology , Dyspnea/etiologyABSTRACT
Severe or repeated hypoglycemia events may favor memory complaints in type 1 diabetes (T1D). Pancreatic islet transplantation (IT) is an alternative option to exogenous insulin therapy in case of labile T1D, implying a maintenance immunosuppression regimen based on sirolimus or mycophenolate, associated with tacrolimus, that may also have neurological toxicity. The objective of this study was to compare a cognitive rating scale Mini-Mental State Examination (MMSE) between T1D patients with or without IT and to identify parameters influencing MMSE. Methods: This retrospective cross-sectional study compared MMSE and cognitive function tests between islet-transplanted T1D patients and nontransplanted T1D controls who were transplant candidates. Patients were excluded if they refused. Results: Forty-three T1D patients were included: 9 T1D patients before IT and 34 islet-transplanted patients (14 treated with mycophenolate and 20 treated with sirolimus). Neither MMSE score (P = 0.70) nor higher cognitive function differed between islet versus non-islet-transplanted patients, whatever the type of immunosuppression. In the whole population (N = 43), MMSE score was negatively correlated to glycated hemoglobin (r = -0.30; P = 0.048) and the time spent in hypoglycemia on the continuous glucose monitoring (r = -0.32; P = 0.041). MMSE score was not correlated to fasting C-peptide level, time spent in hyperglycemia, average blood glucose, time under immunosuppression, duration of diabetes, or beta-score (success score of IT). Conclusions: This first study evaluating cognitive disorders in islet-transplanted T1D patients argues for the importance of glucose balance on cognitive function rather than of immunosuppressive treatment, with a favorable effect of glucose balance improvement on MMSE score after IT.
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BACKGROUND: The main objective of this study was to assess the association between age and physical fitness and motor fitness components according to BMI levels, in men and women separately, and to test if this association is different between BMI levels. METHODS: This cross-sectional study was based on a pre-existing database from the DiagnoHealth battery, a French series of physical fitness and motor fitness tests designed by the Institut des Rencontres de la Forme (IRFO; Wattignies, France). Analyses were perfomed on 6830 women (65.8%) and 3356 men (34.2%) aged from 50 to 80 years. In this French series several physical fitness and motor fitness components were measured: cardiorespiratory fitness (CRF), speed, upper muscular endurance, lower muscular endurance, lower body muscular strengh, agility, balance, and flexibility. From the results of these tests, a specific score named Quotient of Physical Condition was calculated. Associations between age and physical fitness and motor fitness components according to BMI levels were modelized using linear regression for quantitative components, and ordinal logistic regression for ordinal components. Analyses were performed separately for women and men. RESULTS: A significant association of age with physical fitness and motor fitness performance in each BMI levels were observed in women except for lower muscular endurance, muscular strength and flexibility in obese women. A significant association of age with physical fitness and motor fitness performance in each BMI levels were observed in men except for upper/lower muscular endurance and flexibility in obese men. CONCLUSIONS: The present results shown that most of physical fitness and motor fitness decrease with age in women and men. Lower muscular endurance, muscular strength and flexibility did not change in obese women, thereas upper/lower muscular endurance and flexibility did not change in obese men. This finding is particularly revelant for guiding prevention strategies for maintaining physical fitness and motor fitness performance, which is one of the most important component of healthy aging and wellbeing.
Subject(s)
Cardiorespiratory Fitness , Physical Fitness , Male , Humans , Female , Body Mass Index , Cross-Sectional Studies , Muscle Strength , ObesityABSTRACT
OBJECTIVES: To mine the serum proteome of patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) and to detect biomarkers that may assist in earlier and more effective diagnosis and treatment. METHODS: Patients with limited cutaneous SSc, no extensive interstitial lung disease and no PAH-specific therapy were included. They were classified as cases if they had PAH confirmed by right heart catheterisation (RHC) and serum collected on the same day as RHC; and as controls if they had no clinical evidence of PAH. RESULTS: Patients were mostly middle-aged females with anticentromere-associated SSc. Among 1129 proteins assessed by a high-throughput proteomic assay (SOMAscan), only 2 were differentially expressed and correlated significantly with pulmonary vascular resistance (PVR) in SSc-PAH patients (n=15): chemerin (ρ=0.62, p=0.01) and SET (ρ=0.62, p=0.01). To validate these results, serum levels of chemerin were measured by ELISA in an independent cohort. Chemerin levels were confirmed to be significantly higher (p=0.01) and correlate with PVR (ρ=0.42, p=0.04) in SSc-PAH patients (n=24). Chemerin mRNA expression was detected in fibroblasts, pulmonary artery smooth muscle cells (PA-SMCs)/pericytes and mesothelial cells in SSc-PAH lungs by single-cell RNA-sequencing. Confocal immunofluorescence revealed increased expression of a chemerin receptor, CMKLR1, on SSc-PAH PA-SMCs. SSc-PAH serum seemed to induce higher PA-SMC proliferation than serum from SSc patients without PAH. This difference appeared neutralised when adding the CMKLR1 inhibitor α-NETA. CONCLUSION: Chemerin seems an interesting surrogate biomarker for PVR in SSc-PAH. Increased chemerin serum levels and CMKLR1 expression by PA-SMCs may contribute to SSc-PAH pathogenesis by inducing PA-SMC proliferation.
Subject(s)
Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Scleroderma, Systemic , Middle Aged , Female , Humans , Hypertension, Pulmonary/etiology , Proteome , Proteomics , Pulmonary Arterial Hypertension/etiology , Hemodynamics , Biomarkers , Scleroderma, Systemic/complicationsABSTRACT
INTRODUCTION: Total alkaline phosphatase (tALP) levels rise physiologically in maternal serum during pregnancy, and excessively so in certain conditions. However, current reference values are dated, nonlinear, and based on small samples. Factors related to variation in tALP remain unexplained. Thus, our goals in this study were to establish a physiological development curve for tALP within low-risk pregnancies and to evaluate the factors influencing tALP values. METHODS: This was a single-center, retrospective, observational study. All patients who delivered a live singleton infant at our center from January 1, 2011 to May 31, 2019, and had a tALP assay during pregnancy, were included regardless of the gestational age at which the assay was conducted. RESULTS: A total of 2415 pregnancies were included. Median tALP decreased during the first trimester, it increased slightly during the second trimester, and then increased sharply during the third trimester. Factors associated with a significant increase in tALP were chronic histiocytic intervillositis, cholestasis, multiple pregnancies, liver disease, preeclampsia, smoking, and low weight for gestational age. Conversely, gestational diabetes was associated with a discrete decrease in tALP. DISCUSSION: Our large sample allowed establishment of tALP reference curves based on gestational age. To interpret these results more thoroughly, factors that influence tALP rates should be further scrutinized.
Subject(s)
Alkaline Phosphatase , Gestational Age , Female , Humans , Pregnancy , Alkaline Phosphatase/blood , Pregnancy Trimester, Second , Retrospective StudiesABSTRACT
INTRODUCTION AND HYPOTHESIS: To assess the effectiveness, safety and risk factors of failure and complications associated with Adjustable Continence Therapy (ACT®) balloons as a treatment for female stress urinary incontinence (SUI). METHODS: In the present multicentric retrospective study, all women implanted with ACT® balloons between 2000 and 2018 were considered eligible. Effectiveness and safety were assessed at 1 year, and risk factors for failure and complications were sought. The effectiveness was categorized into three distinct groups: Success = maximum 1 pad/day and patient's impression of improvement using a numerical rating scale (NRS) ≥ 8/10; Improvement = decrease of daily pad use and NRS ≥ 5/10; Failure = increase or stability of daily pad use or NRS < 5/10. The intra- and postoperative surgical complications were collected. RESULTS: Over the study period, 281 women were included. Among them, 104 (37.0%), 94 (33.5%) and 83 (29.5%) were categorized as success, improvement, and failure, respectively. Intra-, early and late postoperative complications occurred in 13 (4.6%), 35 (12.5%) and 75 (26.7%) women, respectively. Most early surgical complications were minor according to the Dindo-Clavien classification. Of women that presented a late postoperative surgical complication, 64 (22.8%) underwent an explantation performed under local or general anesthesia without associated sequalae. CONCLUSIONS: The short-term effectiveness associated with ACT® balloons, their minimally invasive implantation and the frequent but easily manageable and sequelae-free complications suggest that they should be part of the therapeutic arsenal for female SUI.
Subject(s)
Urinary Incontinence, Stress , Urinary Sphincter, Artificial , Humans , Female , Male , Urinary Incontinence, Stress/surgery , Urinary Incontinence, Stress/etiology , Treatment Outcome , Retrospective Studies , Prostheses and Implants , Risk Factors , Urinary Sphincter, Artificial/adverse effectsABSTRACT
Diabetes mellitus (DM) is a common comorbidity among cancer patients, but its impact on chemotherapy tolerance has not been widely studied. We aimed to compare the occurrence of severe grade 3/4 adverse events (G3/4 AEs) within 90 days of starting chemotherapy between patients with and without diabetes. We conducted a retrospective single-center study in Lille University Hospital Oncology Department, France. Patients who received the first cycle of chemotherapy for gastrointestinal, gynecological or cancer of unknown primary source between 1 May 2013 and 1 May 2016, were included. Overall, 609 patients were enrolled: 490 patients without diabetes (80.5%) and 119 patients with diabetes (19.5%). Within 90 days of starting chemotherapy, patients with diabetes had a significantly higher occurrence of AEs G3/4 compared to those with no diabetes (multivariate odds ratio [OR]: 1.57 [1.02-2.42], P = .04). More frequent G3/4 AEs in patients with diabetes were infection (26%), hematological disorders (13%), endocrine disorders (13%) and deterioration of the general condition (13%). In the year following the beginning of chemotherapy, patients with diabetes were twice as likely to be hospitalized as those without diabetes (univariate OR: 2.1 [1.40-3.15], P = .0003). After multivariate adjustment, diabetes was no longer significantly associated with the risk of hospitalization (P = .051). There were no differences between patients with and without diabetes regarding dose reduction and chemotherapy treatment delays (P = .61 and P = .30, respectively). Our study suggests the need for better consideration of DM in the personalized care plan to improve chemotherapy tolerance and quality of life of patients with DM.
Subject(s)
Diabetes Mellitus , Neoplasms , Humans , Retrospective Studies , Quality of Life , Diabetes Mellitus/epidemiology , Neoplasms/drug therapy , HospitalizationABSTRACT
Introduction: Global lockdown in the context of the coronavirus disease 2019 (COVID-19) pandemic is an unprecedented experience. We report here the results of an anonymous questionnaire-based survey on the healthcare and control of chronic IMIDs (chronic immune-mediated inflammatory diseases) within the IMMINENT network during the French lockdown (March 17, 2020-May 11, 2020) and the 2-month period following the end of the lockdown (July 11, 2020). Methods: Two anonymous questionnaires were sent by email to 4500 patients who were followed in a university hospital for an IMID in the departments of gastroenterology, rheumatology, dermatology, pneumology, neurology, and internal medicine. Results: A total of 921/4500 (20.46%) responded to the first survey (impact of the lockdown), and 553/4500 (12.28%) to the second (impact at 2-months post-lockdown). Concerning the impact of the lockdown, 420/915 (45.9%) reported affected follow-up. Similarly, after the lockdown, 248/544 (45.6%) declared a negative impact on their follow-up. The repartition by departments of patients' perception of an altered follow-up during (P = .72) and at the end of the lockdown (P = .77) was not statistically different. Our study highlighted the effects of the COVID-19 pandemic and the restriction measures implemented on the self-reported impact felt by patients on the follow-up of their chronic IMIDs without significant differences among all departments. Conclusion: Our study is original by showing that patients, whatever the type of IMID, shared this same negative perception. This transdisciplinary study demonstrated the importance of a collaborative network among all departments.
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Autoantibodies (Aabs) are frequent in systemic sclerosis (SSc). Although recognized as potent biomarkers, their pathogenic role is debated. This study explored the effect of purified immunoglobulin G (IgG) from SSc patients on protein and mRNA expression of dermal fibroblasts (FBs) using an innovative multi-omics approach. Dermal FBs were cultured in the presence of sera or purified IgG from patients with diffuse cutaneous SSc (dcSSc), limited cutaneous SSc or healthy controls (HCs). The FB proteome and transcriptome were explored using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and microarray assays, respectively. Proteomic analysis identified 3,310 proteins. SSc sera and purified IgG induced singular protein profile patterns. These FB proteome changes depended on the Aab serotype, with a singular effect observed with purified IgG from anti-topoisomerase-I autoantibody (ATA) positive patients compared to HC or other SSc serotypes. IgG from ATA positive SSc patients induced enrichment in proteins involved in focal adhesion, cadherin binding, cytosolic part, or lytic vacuole. Multi-omics analysis was performed in two ways: first by restricting the analysis of the transcriptomic data to differentially expressed proteins; and secondly, by performing a global statistical analysis integrating proteomics and transcriptomics. Transcriptomic analysis distinguished 764 differentially expressed genes and revealed that IgG from dcSSc can induce extracellular matrix (ECM) remodeling changes in gene expression profiles in FB. Global statistical analysis integrating proteomics and transcriptomics confirmed that IgG from SSc can induce ECM remodeling and activate FB profiles. This effect depended on the serotype of the patient, suggesting that SSc Aab might play a pathogenic role in some SSc subsets.
Subject(s)
Immunoglobulin G , Scleroderma, Systemic , Autoantibodies , Chromatography, Liquid , Fibroblasts/metabolism , Humans , Proteome/metabolism , Proteomics , Tandem Mass SpectrometryABSTRACT
BACKGROUND: There is little consensus on the best treatment algorithm for unstable severe slipped capital femoral epiphysis (SCFE). Subcapital osteotomy, which is one of the surgical options, is performed either anteriorly (anterior cuneiform osteotomy, CO) or laterally with trochanteric osteotomy (Dunn procedure, DP). The CO is technically easier and decreases operating time. Moreover, because the DP was the standard in our department before it was replaced by the CO, we had a series of consecutive patients. Therefore, we did a retrospective case-control study in unstable, severe SCFEs treated by CO versus DP, which is to our knowledge the first one aiming to compare: (1) postoperative complications and in particular avascular necrosis, (2) functional outcome, (3) radiologic findings. HYPOTHESIS: CO is less or just as likely to cause avascular necrosis and has the same clinical and radiologic findings as DP. METHODS: A total of 41 patients (24 girls, i.e. 58.5%) were included between 2005 and 2018: 23 in the CO group and 18 in the DP group. The median age was 12.9 years (range, 11.5-14.9) and the median slip angle 70Ì (range, 62.5Ì-80Ì) with a median follow-up of 3 years (range, 2-4). Preoperative, intraoperative, and postoperative clinical and radiologic parameters (Southwick and alpha angles, and femoral head-neck offset) were analyzed, and all complications were documented. RESULTS: Two (8.7%) cases of avascular necrosis were reported in the CO group and 6 (33.3%) in the DP group (p=.11), with an overall rate of avascular necrosis of 19.5% (8/41). Five out of the 41 patients (12.2%) underwent a total hip arthroplasty: 1/23 (4.3%) in the CO group and 4/18 (22.2%) in the DP group (p=.16). Two (9.5%) patients in the CO group and 7 (38.9%) in the DP group developed postoperative limping before any arthroplasty was performed (p=.055). The alpha angle at follow-up (54±6.1Ì vs. 59.1±7.2Ì; p=.027), Oxford hip score at follow-up (17/60 [range, 14-20] vs. 23.5 [range, 19-27]) (p=.021), operating time (132 min [range, 103-166] vs. 199.5 min [range, 142-215]) (p=.011) and intraoperative bleeding (250 mL [range, 100-350] vs. 300 mL [range, 197-450]) (p=.088) were more favorable in the CO group than in the DP group. CONCLUSIONS: The CO has similar results to DP in the surgical management of unstable severe SCFE. LEVEL OF EVIDENCE: III; retrospective comparative study.
Subject(s)
Slipped Capital Femoral Epiphyses , Case-Control Studies , Child , Epiphyses , Female , Follow-Up Studies , Humans , Male , Necrosis , Osteotomy/methods , Radiography , Retrospective Studies , Slipped Capital Femoral Epiphyses/diagnostic imaging , Slipped Capital Femoral Epiphyses/surgery , Treatment OutcomeABSTRACT
OBJECTIVE: It is unclear whether glycated haemoglobin (HbA1c) has utility in predicting adverse outcomes in gestational diabetes mellitus (GDM). The aims of the study were to examine the predictive value of HbA1c at GDM diagnosis with adverse pregnancy outcomes. RESEARCH DESIGN AND METHODS: This was a cohort study of 4,383 women with GDM between 2011 and 2018. We assessed the association of HbA1c with pregnancy outcomes using logistic regression models before and after adjustment for predefined risk factors of GDM. We examined these associations considering HbA1c as categorical variables using five pre-specified HbA1c classes: and as a continuous variable. RESULTS: An HbA1c ≥ 5.6% (38 mmol/mol) identified women with at greater risk for macrosomia: odds ratio (OR) [95% confidence interval] = 2.12 [1.29; 3.46] for HbA1c = 5.6-5.9% and 2.06 [1.14; 3.70] for HbA1c > 5.9% versus HbA1c ≤ 4.5% (26 mmol/mol). Similarly, HbA1c ≥ 5.6% (38 mmol/mol) was associated with greater risk for caesarean: 1.64 [1.06; 2.53] for HbA1c = 5.6-5.9% and 1.58 [0.93; 2.7] for HbA1c > 5.9% (41 mmol/mol) versus HbA1c ≤ 4.5% (26 mmol/mol). Using HbA1c ≤ 4.5% (26 mmol/mol) as reference category, HbA1c > 5.9% (41 mmol/mol) increased the OR of preterm delivery to 3.33 [1.27; 8.71]. HbA1c remained significant for Adverse Pregnancy Outcome Composite after adjustment (P < 0.0001). DISCUSSION: Our finding suggests that a single HbA1c reading may be a useful pragmatic tool to identify women at risk. Such identification may be a useful guide for identifying and applying preventative treatment for women at increased risk.
Subject(s)
Diabetes, Gestational , Pregnancy Complications , Cohort Studies , Diabetes, Gestational/diagnosis , Diabetes, Gestational/epidemiology , Female , Fetal Macrosomia/etiology , Glycated Hemoglobin/analysis , Humans , Infant, Newborn , Pregnancy , Pregnancy Outcome/epidemiologyABSTRACT
Objective: The need of luteal support after FET is no longer to be proven. Different routes of progesterone administration are available with interindividual differences in metabolization and serum progesterone levels, the latter being highly correlated with pregnancy and delivery rates. The administration of 2 different routes of progestogen significantly improves success rates in FET. The aim of the current study was to investigate the added value to combine intramuscular administration of progesterone to dydrogesterone in fresh embryo transfer. Methods: This is a retrospective study from prospectively collected data. Patient, aged between 18 and 43 years old, had received a fresh blastocyst transfer between January 2021 and June 2021. In the first group, all patients received only oral dydrogesterone 10mg, three times a day, beginning the evening of oocyte retrieval. In the second group, patients received, in addition to dydrogesterone, a weekly intramuscular injection of progesterone started the day of embryo transfer. Primary endpoint was ongoing pregnancy rate. Results: 171 fresh single blastocyst transfers have been performed during this period. 82 patients were included in "dydrogesterone only" and 89 patients in "dydrogesterone + IM". Our two groups were comparable except for body mass index. After adjustment on BMI, our two groups were comparable regarding implantation rate, early pregnancy rate (46.1 versus 54.9, OR 1.44 [0.78; 2.67], p=0.25) miscarriage rate, ongoing pregnancy rate (30.3 versus 43.9, OR 1.85 [0.97; 3.53] p= 0.06). Conclusion: Using systematically long acting intramuscular progesterone injection in addition to oral dydrogesterone as luteal phase support seems to have no significant impact on IVF outcomes when a single fresh blastocyst transfer is performed.
Subject(s)
Dydrogesterone , Progesterone , Pregnancy , Female , Humans , Pilot Projects , Luteal Phase , Retrospective Studies , Administration, Oral , Embryo TransferABSTRACT
CONTEXT: Despite optimization of metabolic balance during pregnancy in type 1 diabetes (T1D), maternal-fetal complications remain higher than in the background population. OBJECTIVE: We examined whether there is an association between glycated hemoglobin (HbA1c) levels and these complications. METHODS: Retrospective study of pregnancies in 678 T1D subjects at Lille Hospital (1997-2019). The association between variations in HbA1c levels and complications was examined. The composite criterion (CC) was defined as having at least 1 of the following complications: prematurity, pre-eclampsia, large for gestational age (LGA), small for gestational age (SGA), or cesarean section. RESULTS: Among the 678 births, median preconception HbA1c was 7.2% (55 mmol/mol), 361 were LGA (56%), 29 were SGA (4.5%), and 504 were births without preterm delivery (76.1%). The CC occurred in 81.8%. Higher HbA1c during the first trimester was associated with the CC (OR 1.04; 95% CI 1.02-1.06 per 0.1% increase; Pâ <â .001). Higher HbA1c during the third trimester was associated with the CC (OR 1.07; 95% CI 1.03-1.10 per 0.1% increase; Pâ <â .001). The group defined by a first trimester Hba1c >6.5% (48 mmol/mol) and a third trimester HbA1c <6% was associated with an increased rate of the CC (OR 2.81; 95% CI 1.01-7.86) and an increased rate of LGA (OR 2.20; 95% CI 1.01- 4.78). CONCLUSION: Elevated HbA1c is associated with maternal-fetal complications. Despite optimization of metabolic balance during the third trimester, for patients with early glycemic imbalance the risk of LGA persists.
Subject(s)
Diabetes Mellitus, Type 1/complications , Fetal Macrosomia/epidemiology , Glycated Hemoglobin/analysis , Pre-Eclampsia/epidemiology , Pregnancy in Diabetics/blood , Adult , Cesarean Section/statistics & numerical data , Diabetes Mellitus, Type 1/blood , Female , Fetal Macrosomia/etiology , Follow-Up Studies , Humans , Infant, Newborn , Infant, Small for Gestational Age , Pre-Eclampsia/etiology , Pregnancy , Pregnancy Outcome , Retrospective Studies , Risk Assessment/methods , Risk Assessment/statistics & numerical dataABSTRACT
BACKGROUND: In many clinical applications, evolution of a longitudinal marker is censored by an event occurrence, and, symmetrically, event occurrence can be influenced by the longitudinal marker evolution. In such frameworks joint modeling is of high interest. The Joint Latent Class Model (JLCM) allows to stratify the population into groups (classes) of patients that are homogeneous both with respect to the evolution of a longitudinal marker and to the occurrence of an event; this model is widely employed in real-life applications. However, the finite sample-size properties of this model remain poorly explored. METHODS: In the present paper, a simulation study is carried out to assess the impact of the number of individuals, of the censoring rate and of the degree of class separation on the finite sample size properties of the JLCM. A real-life application from the neurology domain is also presented. This study assesses the precision of class membership prediction and the impact of covariates omission on the model parameter estimates. RESULTS: Simulation study reveals some departures from normality of the model for survival sub-model parameters. The censoring rate and the number of individuals impact the relative bias of parameters, especially when the classes are weakly distinguished. In real-data application the observed heterogeneity on individual profiles in terms of a longitudinal marker evolution and of the event occurrence remains after adjusting to clinically relevant and available covariates; CONCLUSION: The JLCM properties have been evaluated. We have illustrated the discovery in practice and highlights the usefulness of the joint models with latent classes in this kind of data even with pre-specified factors. We made some recommendations for the use of this model and for future research.
Subject(s)
Amyotrophic Lateral Sclerosis , Amyotrophic Lateral Sclerosis/diagnosis , Bias , Computer Simulation , Humans , Longitudinal Studies , Models, StatisticalABSTRACT
PURPOSE/INTRODUCTION: A Fracture Liaison Service (FLS) was set up at Lille University Hospital in 2016. The purpose of this study was to assess persistence with osteoporosis treatment in patients from the FLS over a period of 1 year, and to determine predictors of discontinuation. METHODS: The study population comprised adults of both genders, aged 50 or over, admitted to Lille University Hospital between January 2016 and January 2019 for a low-trauma fracture and managed in our FLS. Outcomes included (1) persistence rate at 1 year after treatment initiation, (2) persistence rate at 2 years after treatment initiation, (3) persistence rate at 1 and 2 years after treatment initiation according to type of treatment, (4) predictors of non-persistence, and (5) reasons for discontinuing treatment over 1 year after initiation. Persistence was determined using the Kaplan-Meier method. RESULTS: In all, 1224 patients (≥50 years old) with a recent history of low-trauma fracture (≤12 months) were identified. Of these, 380 patients - 79.2% female; mean (SD) age 76 (11) years - were seen at the FLS. In those 380 patients, 410 fractures were found and 360 of them (87.8%) were major fractures, breaking down as follows: vertebra (44%), hip (19%), proximal humerus (10%), and pelvis (8%). Osteoporosis treatment was prescribed for 367 (96.6%) patients and 275 of them began the prescribed treatment. The following anti-osteoporosis drugs were prescribed: zoledronic acid (n=150, 54.5%), teriparatide (n=63, 22.9%), and denosumab (n=39, 14.2%). Oral bisphosphonates were prescribed for a few patients (n=23, 8.4%). Persistence with osteoporosis medication (any class) was estimated at 84.1% (95% CI: 79.1% to 88.1%) at 12-month follow-up, and dropped to 70.3% (95% CI: 63.7% to 75.9%) at 24 months. When drug-specific analyses were performed using the Kaplan-Meier method, persistence rates at 12 and 24 months were found to be higher with denosumab than with any other treatment. Independent predictors of non-persistence at 12 months were 'follow-up performed by a general practitioner (GP)' - Odds Ratio (OR) for GP vs. FLS = 3.68; 95% CI, 1.52 to 8.90, p=0.004 - and 'treatment with zoledronic acid' - OR for zoledronic acid vs. denosumab = 3.39; 95% CI, 1.21 to 9.50, p=0.019; OR for zoledronic acid vs. teriparatide = 8.86; 95% CI, 1.15 to 68.10, p=0.035. CONCLUSIONS: This study provides evidence of the success of our FLS in terms of long-term persistence with osteoporosis treatments. However, osteoporosis treatment initiation still needs to be improved.
Subject(s)
Bone Density Conservation Agents , Osteoporosis , Osteoporotic Fractures , Adult , Aged , Bone Density Conservation Agents/therapeutic use , Female , Hospitals , Humans , Male , Middle Aged , Osteoporosis/drug therapy , Osteoporosis/epidemiology , Osteoporotic Fractures/drug therapy , Osteoporotic Fractures/epidemiology , SpineABSTRACT
INTRODUCTION: Reports of elevated bone mass (EBM) on routine DXA scanning are not infrequent. However, epidemiological studies of EBM are few in number and definition thresholds variable. The purpose of this study was to assess the prevalence and causes of EBM in the general population referred to a single university hospital - catering for a population of 4 million inhabitants - for DXA scanning. MATERIAL AND METHODS: DXA databases were initially searched for individuals with a bone mineral density (BMD) Z-score ≥+4 at any site in the lumbar spine or hip from April 1st, 2008 to April 30st, 2018. Two Hologic scanners were available at the Lille University Hospital (France). Prevalence of EBM was evaluated, as were causes associated with EBM. RESULTS: At the lumbar spine, 18,229 bone density tests were performed in women and 10,209 in men. At the hip, 17,390 tests were performed in women and 9857 in men. The total number of patients who had at least one bone density test was 14,745, of which 64.2% were female. Of these 14,745 patients, 211 had a Z-score ≥+4 at any site, i.e. a prevalence of 1.43% [1.25%-1.64%]. The DXA scans and medical records of 92 men and 119 women with elevated BMD were reviewed to assess causes. An artefactual cause was found in 164 patients (75%) with EBM (mostly degenerative disease of the spine), and an acquired cause of focal EBM was found in only 2 patients, both of whom had sclerotic bone metastases from prostate cancer. An acquired cause of generalized EBM was found in 32 patients (15%), the vast majority of whom had renal osteodystrophy (n = 11), followed by hematological disorders (n = 9; e.g. myeloproliferative syndromes and mastocytosis) and diffuse bone metastases from solid cancer (n = 5). Of the remaining causes, rare hereditary diseases (e.g. osteopetrosis ) and unexplained EBM were found in 10 and 6 cases respectively. CONCLUSION: The prevalence of EBM (Z-score ≥+4 at any site) was 1.43% [1.25%-1.64%]. In nearly all instances (97.1%) the explanation for EBM could be found in the medical record and through conventional investigations. This study suggests that the main cause of EBM is degenerative disease of the spine. Further studies are needed to differentiate artefactual EBM from hereditary or acquired EBM, and to investigate unexplained EBM. Genetic testing may prove useful in elucidating rare unknown causes.
Subject(s)
Bone Density , Lumbar Vertebrae , Absorptiometry, Photon , Female , France , Humans , Male , PrevalenceABSTRACT
The primary objective of this study was to establish sex- and age-specific physical fitness percentiles for French children. The secondary aim was to assess sex, weight status, and age differences for physical fitness levels in French children. A sample of 31 484 children (16 023 boys, 15 461 girls) aged 6-11 years participated in the Diagnoform programme. Cardiorespiratory fitness, muscular endurance, speed, flexibility, and agility were assessed in this national programme. Percentile values were estimated as a function of age stratified by sex using a parametric method providing smooth centile curves and explicit formulae for the centile estimates. Values from the 10th to the 90th percentile are reported. The influence of body weight according to sex on the physical fitness level was also examined using an analysis of covariance adjusted for age. Physical fitness levels were slightly better in boys, except for agility and flexibility, in which girls performed better (Cohen's coefficient, 0.20-0.45; P < .001). All physical fitness tests were significantly associated with age (P < .0001). In general, overweight and obese children had a significantly poorer physical fitness level compared with their normal-weight counterparts (P < .05). No difference was found between thin and normal-weight boys and girls, except for agility (P < .05). Reference values provide normative data for French children, and these data should be useful for identifying special needs for appropriate intervention programmes.