Why harmonization is needed when using FDG PET/CT as a prognosticator: demonstration with EARL-compliant SUV as an independent prognostic factor in lung cancer.

BACKGROUND: To determine EARL-compliant prognostic SUV thresholds in a mature cohort of patients with locally advanced NSCLC, and to demonstrate how detrimental it is to use a threshold determined on an older-generation PET system with a newer PET/CT machine, and vice versa, or to use such a threshold with non-harmonized multicentre pooled data. MATERIALS AND METHODS: This was a single-centre retrospective study including 139 consecutive stage IIIA-IIIB patients. PET data were acquired as per the EANM guidelines and reconstructed with unfiltered point spread function (PSF) reconstruction. Subsequently, a 6.3 mm Gaussian filter was applied using the EQ.PET (Siemens Healthineers) methodology to meet the EANM/EARL harmonizing standards (PSFEARL). A multicentre study including non-EARL-compliant systems was simulated by randomly creating four groups of patients whose images were reconstructed with unfiltered PSF and PSF with Gaussian post-filtering of 3, 5, and 10 mm. Identification of optimal SUV thresholds was based on a two-fold cross-validation process that partitioned the overall sample into learning and validation subsamples. Proportional Cox hazards models were used to estimate age-adjusted and multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals. Kaplan-Meier curves were compared using the log rank test. RESULTS: Median follow-up was 28 months (1-104 months). For the whole population, the estimated overall survival rate at 36 months was 0.39 [0.31-0.47]. The optimal SUVmax cutoff value was 25.43 (95% CI: 23.41-26.31) and 8.47 (95% CI: 7.23-9.31) for the PSF and for the EARL-compliant dataset respectively. These SUVmax cutoff values were both significantly and independently associated with lung cancer mortality; HRs were 1.73 (1.05-2.84) and 1.92 (1.16-3.19) for the PSF and the EARL-compliant dataset respectively. When (i) applying the optimal PSF SUVmax cutoff on an EARL-compliant dataset and the optimal EARL SUVmax cutoff on a PSF dataset or (ii) applying the optimal EARL compliant SUVmax cutoff to a simulated multicentre dataset, the tumour SUVmax was no longer significantly associated with lung cancer mortality. CONCLUSION: The present study provides the PET community with an EARL-compliant SUVmax as an independent prognosticator for advanced NSCLC that should be confirmed in a larger cohort, ideally at other EARL accredited centres, and highlights the need to harmonize PET quantitative metrics when using them for risk stratification of patients.

Correction to: Why harmonization is needed when using FDG PET/CT as a prognosticator: demonstration with EARL-compliant SUV as an independent prognostic factor in lung cancer.

An error occurred in the labelling of Fig. 3, where math symbols for SUV thresholds were inverted in panel b when the EARL threshold was applied to the PSF dataset and vice versa. This figure should read as follows: Fig. 3: Prognostic value of tumour SUVmax.

Resistance to antibiotics: limit theorems for a stochastic SIS model structured by level of resistance.

The rise of bacterial resistance to antibiotics is a major Public Health concern. It is the result of two interacting processes: the selection of resistant bacterial strains under exposure to antibiotics and the dissemination of bacterial strains throughout the population by contact between colonized and uncolonized individuals. To investigate the resulting time evolution of bacterial resistance, Temime et al. (Emerg Infect Dis 9:411-417, 2003) developed a stochastic SIS model, which was structured by the level of resistance of bacterial strains. Here we study the asymptotic properties of this model when the population size is large. To this end, we cast the model within the framework of measure valued processes, using point measures to represent the pattern of bacterial resistance in the compartments of colonized individuals. We first show that the suitably normalized model tends in probability to the solution of a deterministic differential system. Then we prove that the process of fluctuations around this limit tends in law to a Gaussian process in a space of distributions. These results, which generalize those of Kurtz (CBMS-NSF regional conference series in applied mathematics, vol 36. Society for Industrial and Applied Mathematics (SIAM), Philadelphia, 1981, chap. 8) on SIR models, support the validity of the deterministic approximation and quantify the rate of convergence.

Patient, clinical, surgical, and institutional factors associated with length of stay in scheduled degenerative thoracolumbar spine surgery: National Multicenter Cohort Analysis from the Canadian Spine Outcomes and Research Network.

OBJECTIVE: Length of stay (LOS) is a contributor to costs and resource utilization. The primary goal of this study was to identify patient, clinical, surgical, and institutional variables that influence LOS after elective surgery for thoracolumbar degenerative pathology. The secondary objective was to examine variability in LOS and institutional strategies used to decrease LOS. METHODS: This is a retrospective study of prospectively collected data from a multicentric cohort enrolled in the Canadian Spine Outcomes and Research Network (CSORN) between January 2015 and October 2020 who underwent elective thoracolumbar surgery (discectomy [1 or 2 levels], laminectomy [1 or 2 levels], and posterior instrumented fusion [up to 5 levels]). Prolonged LOS was defined as LOS greater than the median. Logistic regression models were used to determine factors associated with prolonged LOS for each procedure. A survey was sent to the principal investigators of the participating healthcare institutions to understand institutional practices that are used to decrease LOS. RESULTS: A total of 3700 patients were included (967 discectomies, 1094 laminectomies, and 1639 fusions). The median LOSs for discectomy, laminectomy, and fusion were 0.0 (IQR 1.0), 1.0 (IQR 2.0), and 4.0 (IQR 2.0) days, respectively. On multivariable analysis, predictors of prolonged LOS for discectomy were having more leg pain, higher Oswestry Disability Index (ODI) scores, symptom duration more than 2 years, having undergone an open procedure, occurrence of an adverse event (AE), and treatment at an institution without protocols to reduce LOS (p < 0.05). Predictors of prolonged LOS for laminectomy were increased age, living alone, higher ODI scores, higher BMI, open procedures, longer operative time, AEs, and treatment at an institution without protocols to reduce LOS (p < 0.05). For posterior instrumented fusion, predictors of prolonged LOS were older age, living alone, more comorbidities, higher ODI scores, longer operative time, AEs, and treatment at an institution without protocols to reduce LOS (p < 0.05). The laminectomy group had the largest variability in LOS (SD 4.4 days, range 0-133 days). Three hundred fifty-four patients (22%) had an LOS above the 75th percentile. Ten institutions (53%) had either Enhanced Recovery After Surgery or standardized protocols in place. CONCLUSIONS: Among the factors identified in this study, worse baseline ODI scores, experiencing AEs, and treatment at an institution without protocols aimed at reducing LOS were predictive of prolonged LOS in all surgical groups. The laminectomy group had the largest variability in LOS.

Low-back pain after lumbar discectomy for disc herniation: what can you tell your patient?

OBJECTIVE: Lumbar discectomy (LD) is frequently performed to alleviate radicular pain resulting from disc herniation. While this goal is achieved in most patients, improvement in low-back pain (LBP) has been reported inconsistently. The goal of this study was to characterize how LBP evolves following discectomy. METHODS: The authors performed a retrospective analysis of prospectively collected patient data from the Canadian Spine Outcomes and Research Network (CSORN) registry. Patients who underwent surgery for lumbar disc herniation were eligible for inclusion. The primary outcome was a clinically significant reduction in the back pain numerical rating scale (BPNRS) assessed at 12 months. Binary logistic regression was used to model the relationship between the primary outcome and potential predictors. RESULTS: There were 557 patients included in the analysis. The chief complaint was radiculopathy in 85%; 55% of patients underwent a minimally invasive procedure. BPNRS improved at 3 months by 48% and this improvement was sustained at all follow-ups. LBP and leg pain improvement were correlated. Clinically significant improvement in BPNRS at 12 months was reported by 64% of patients. Six factors predicted a lack of LBP improvement: female sex, low education level, marriage, not working, low expectations with regard to LBP improvement, and a low BPNRS preoperatively. CONCLUSIONS: Clinically significant improvement in LBP is observed in the majority of patients after LD. These data should be used to better counsel patients and provide accurate expectations about back pain improvement.

Temporal variability and social heterogeneity in disease transmission: the case of SARS in Hong Kong.

The extent to which self-adopted or intervention-related changes in behaviors affect the course of epidemics remains a key issue for outbreak control. This study attempted to quantify the effect of such changes on the risk of infection in different settings, i.e., the community and hospitals. The 2002-2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong, where 27% of cases were healthcare workers, was used as an example. A stochastic compartmental SEIR (susceptible-exposed-infectious-removed) model was used: the population was split into healthcare workers, hospitalized people and general population. Super spreading events (SSEs) were taken into account in the model. The temporal evolutions of the daily effective contact rates in the community and hospitals were modeled with smooth functions. Data augmentation techniques and Markov chain Monte Carlo (MCMC) methods were applied to estimate SARS epidemiological parameters. In particular, estimates of daily reproduction numbers were provided for each subpopulation. The average duration of the SARS infectious period was estimated to be 9.3 days (+/-0.3 days). The model was able to disentangle the impact of the two SSEs from background transmission rates. The effective contact rates, which were estimated on a daily basis, decreased with time, reaching zero inside hospitals. This observation suggests that public health measures and possible changes in individual behaviors effectively reduced transmission, especially in hospitals. The temporal patterns of reproduction numbers were similar for healthcare workers and the general population, indicating that on average, an infectious healthcare worker did not infect more people than any other infectious person. We provide a general method to estimate time dependence of parameters in structured epidemic models, which enables investigation of the impact of control measures and behavioral changes in different settings.

[Retrospective study: Late surgery post chemotherapy versus after 3-4 cures in treatment of advanced ovarian cancer]. / Étude rétrospective : chirurgie d'intervalle tardive post chimiothérapie versus après 3­4 cures dans le cadre de la prise en charge d'un cancer de l'ovaire localement avancé non opérable d'emblée.

INTRODUCTION: Treatment in locally advanced ovarian cancer is optimal surgery followed by chemotherapy. Patients with significant tumor spread, OMS>2, age>75 years old are poor candidates for aggressive primary surgery. Interval surgery, after neo-adjuvant chemotherapy, aims to achieve more complete surgery, increase survival, and reduce surgical morbidity. The primary endpoint was progression-free survival. Secondary outcomes were overall survival and postoperative morbidity and mortality. METHOD: This is a retrospective study conducted in 2 French referral centers between January 2000 and December 2015. Patients who could not benefit from a complete initial surgery were operated after 3 cures of chemotherapy at the François Baclesse center and after least 5 cures at the center René Gauducheau. RESULTS: The population analyzed included 104 patients, 43 (41.0%) patients treated at the René Gauducheau center (group 1) and 61 (59.0%) patients treated at the François Baclesse center (group 2). Progression-free and overall survival were similar between the 2 groups, they were, respectively, 15.9 months and 34 months in group 1 vs. 15.4 months and 37.6 months in group 2 (P=0.72; P=0.65). Mean hospital stay and postoperative morbidity were similar in both groups. CONCLUSION: For weak patients, to limit invasive surgery, doing more than 5 courses of chemotherapy may be a reasonable option.

Safety Priorities and Underestimations in Recreational Scuba Diving Operations: A European Study Supporting the Implementation of New Risk Management Programmes.

Introduction: Scuba diving is an important marine tourism sector, but requires proper safety standards to reduce the risks and increase accessibility to its market. To achieve safety goals, safety awareness and positive safety attitudes in recreational scuba diving operations are essential. However, there is no published research exclusively focusing on scuba divers' and dive centres' perceptions toward safety. This study assessed safety perceptions in recreational scuba diving operations, with the aim to inform and enhance safety and risk management programmes within the scuba diving tourism industry. Materials and Methods: Two structured questionnaire surveys were prepared by the organisation Divers Alert Network and administered online to scuba diving operators in Italy and scuba divers in Europe, using a mixture of convenience and snowball sampling. Questions in the survey included experience and safety offered at the dive centre; the buddy system; equipment and accessories for safe diving activities; safety issues in the certification of new scuba divers; incidents/accidents; and attitudes toward safety. Results: 91 scuba diving centres and 3,766 scuba divers participated in the study. Scuba divers gave importance to safety and the responsiveness of service providers, here represented by the dive centres. However, they underestimated the importance of a personal emergency action/assistance plan and, partly, of the buddy system alongside other safety procedures. Scuba divers agreed that some risks, such as those associated with running out of gas, deserve attention. Dive centres gave importance to aspects such as training and emergency action/assistance plans. However, they were limitedly involved in safety campaigning. Dive centres' perceptions of safety in part aligned with those of scuba divers, with some exceptions. Conclusion: Greater responsibility is required in raising awareness and educating scuba divers, through participation in prevention campaigns and training. The study supports the introduction of programmes aiming to create a culture of safety among dive centres and scuba divers. Two examples, which are described in this paper, include the Hazard Identification and Risk Assessment protocol for dive centres and scuba divers, and the Diving Safety Officer programme to create awareness, improve risk management, and mitigate health and safety risks.

S. pneumoniae transmission according to inclusion in conjugate vaccines: Bayesian analysis of a longitudinal follow-up in schools.

BACKGROUND: Recent trends of pneumococcal colonization in the United States, following the introduction of conjugate vaccination, indicate that non-vaccine serotypes tend to replace vaccine serotypes. The eventual extent of this replacement is however unknown and depends on serotype-specific carriage and transmission characteristics. METHODS: Here, some of these characteristics were estimated for vaccine and non-vaccine serotypes from the follow-up of 4,488 schoolchildren in France in 2000. A Bayesian approach using Markov chain Monte Carlo data augmentation techniques was used for estimation. RESULTS: Vaccine and non-vaccine serotypes were found to have similar characteristics: the mean duration of carriage was 23 days (95% credible interval (CI): 21, 25 days) for vaccine serotypes and 22 days (95% CI: 20, 24 days) for non-vaccine serotypes; within a school of size 100, the Secondary Attack Rate was 1.1% (95% CI: 1.0%, 1.2%) for both vaccine and non-vaccine serotypes. CONCLUSION: This study supports that, in 3-6 years old children, no competitive advantage exists for vaccine serotypes compared to non-vaccine serotypes. This is an argument in favour of important serotype replacement. It would be important to validate the result for infants, who are known to be the main reservoir in maintaining transmission. Overall reduction in pathogenicity should also be taken into account in forecasting the future burden of pneumococcal colonization in vaccinated populations.

Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT): Characteristics, treatment and outcome in 251 cases from the literature.

BACKGROUND: Steroid-responsive encephalopathy and associated autoimmune thyroiditis (SREAT) is characterized by encephalopathy and the presence of antithyroid antibodies. We describe the clinical presentation, outcome and treatments for SREAT by a systematic review of the literature. METHODS: MEDLINE via PubMed, Web of Science and the Cochrane Library were searched for articles published until 2015. Inclusion criteria were unexplained encephalopathy with antithyroid antibodies. RESULTS: We found reports of 251 patients (median age 52years [range 18-86], 73% females, 80 [32%] with preexisting thyroiditis). Patients presented encephalitis signs with convulsions (n=117; 47%), confusion (n=115, 46%), speech disorder (n=91, 37%), memory impairment (n=107, 43%), gait disturbance (n=67, 27%) and persecutory delusions (n=61, 25%). Twenty-eight patients (11%) presented progressive memory impairment and 26 (10%) isolated psychiatric disorders. In serum, 34% of patients were positive for anti-thyroid peroxidase (TPO) antibodies, 7% for anti-thyroglobulin (TG) antibodies, and 69% both. Thyroid-stimulating hormone levels were usually normal, at 2 UI/ml [0.001-205]. Cerebrospinal fluid from 10/53 patients (19%) was positive for anti-TPO antibodies, 2/53 (4%) anti-TG antibodies and 28 (53%) both. Electroencephalography findings were abnormal for 82% of patients, showing diffuse slowing consistent with encephalopathy (70%) or epileptic activity (14%). The first-line treatment was steroids in 193 patients and other immunosuppressive drugs in 10 cases. At a median follow-up of 12months [range 0.2-110], 91% of patients showed complete or partial neurological response, with anti-TPO and -TG antibody titers at 347 UI/ml [0-825,000] and 110 UI/ml [0-50,892], respectively. During follow-up, 40 patients (16%) experienced at least one relapse. Relapse was more frequent in patients with initial coma (26% vs 13%, p=0.08). CONCLUSION: The diagnosis of SREAT should be suspected in case of encephalopathy without obvious cause, to quickly start corticosteroid treatment. The exact modalities of treatment must be defined.

Sample size calculation should be performed for design accuracy in diagnostic test studies.

BACKGROUND AND OBJECTIVES: Guidelines for conducting studies and reading medical literature on diagnostic tests have been published: Requirements for the selection of cases and controls, and for ensuring a correct reference standard are now clarified. Our objective was to provide tables for sample size determination in this context. STUDY DESIGN AND SETTING: In the usual situation, where the prevalence Prev of the disease of interest is <0.50, one first determines the minimal number Ncases of cases required to ensure a given precision of the sensitivity estimate. Computations are based on the binomial distribution, for user-specified type I and type II error levels. The minimal number N(controls) of controls is then derived so as to allow for representativeness of the study population, according to Ncontrols=Ncases [(1-Prev)/Prev]. RESULTS: Tables give the values of Ncases corresponding to expected sensitivities from 0.60 to 0.99, acceptable lower 95% confidence limits from 0.50 to 0.98, and 5% probability of the estimated lower confidence limit being lower than the acceptable level. CONCLUSION: When designing diagnostic test studies, sample size calculations should be performed in order to guarantee the design accuracy.

Modelling the epidemic of variant Creutzfeldt-Jakob disease in the UK based on age characteristics: updated, detailed analysis.

Incubation period of the new variant Creutzfeldt-Jakob disease (vCJD) from infection to clinical onset and the eventual impact of the disease remain major concerns. Based on i) epidemiological conceptualization of human exposure to BSE contaminated material, ii) exponentially decreasing susceptibility after 15 years of age, and iii) typical incubation period (IP) distributions for time from infection to onset, we have previously estimated mean incubation period and projected number of vCJD cases. In this paper, we investigate the robustness of these estimates with respect to i-iii using the UK's 113 vCJD cases with clinical onset before December 2000. Mean incubation period was estimated at 16.4 years (95% CI 11.4-24.8), 15.9 years (95% CI 11.4-22.0), 14.1 years (95% CI 10.4-24.2) with the log-normal, Gamma and Weibull distributions respectively. Corresponding predictions for the total size of the epidemic ranged from 183 to 304. Maximal susceptibility to infection between 1.3 and 15.9 years and decreasing by 15% per year of age thereafter yielded the best fit. The shape of the IP distribution did not affect the predictions. In summary, within a set of reasonable assumptions, mean incubation period for vCJD ranged from 15 to 20 years, and the eventual impact of vCJD was a few hundred patients.

Suicide and attempted suicide in France: results of a general practice sentinel network, 1999-2001.

The continuous surveillance of suicide and attempted suicide cases was added to the tasks of the French Sentinel Network of General Practitioners (GPs) in 1999. In 2001, 9700 suicides were estimated to have occurred and an estimated 61 500 attempted suicide cases were diagnosed by GPs, representing approximately 40% of cases nationwide. The majority of suicide and attempted suicide cases involved women (67%) and 43% of all cases involved patients aged 25-44 years. The fatality rate increased with age. About 80% of GPs complied with the current recommendation to refer patients who had attempted suicide to hospital.

Evaluating the functional impairment of assault survivors in a judicial context - A retrospective study.

BACKGROUND: The description of traumatic injuries and the outcome on functioning are major items of the evaluation of assault survivors. French law quantifies the seriousness of committed violence through the duration of the victims' inability to fulfil their usual daily activities, in days of 'Total incapacity to work' (TIW). Physicians are provided with a limited number of recommendations. In this study, we searched for determinants of TIW. METHODS: We reviewed 1145 consecutives files of victims evaluated between 10/01/2010 and 11/22/2010. People reporting repeated assaults, or assessed more than 30 days after the facts were excluded. Data collected were: gender, age, TIW, type of traumatic injuries, time to evaluation, patient category, type of assailant, and presence of aggravating factors. Univariate associations with TIW were assessed, while generalised linear models including relevant covariables were proposed. RESULTS: The population (718 men, 427 women, median age 29) included 236 detainees, 74 police officers, and 835 other individuals. Mean duration of TIW was 4.3 days. The time to evaluation was correlated to TIW. Patient category (police officers, detainees, or other individuals), presence of traumatic injuries, and type of assailant were associated with TIW. In patients presenting no evidence of bone fracture, duration of TIW (2.0 days vs. 2.6 and 3.8, p < 0.001) and time to evaluation (10.9 h vs. 21.2 and 58.5, p < 0.001) differed in detainees, police officers, and other individuals. CONCLUSION: We suggest that the outcome of assaults should be evaluated in similar conditions in all victims, including time to evaluation.

Psychotropic drug use among older people in general practice: discrepancies between opinion and practice.

BACKGROUND: The use of psychotropic drugs has increased over recent years in France. GPs are the first prescribers, especially for older patients. AIM: To analyse discrepancies between GPs' opinions and practice when prescribing psychotropic drugs to older patients. SETTING: Postal surveys sent to GPs all over mainland France. DESIGN OF STUDY: Cross-sectional postal study. METHOD: A questionnaire collected data on characteristics of GPs' practices, their opinions about psychotropic drug consumption in older people, and a full description of their last older patient receiving a psychotropic drug and seen last by the GP on that particular day. RESULTS: A total of 350 participating GPs saw 2498 patients aged > or =65 years. Among these patients, the prevalence of psychotropic use was 32.1% (803/2498) for anxiolytics/hypnotics, and 17.5% for antidepressants (438/2498). A total of 91% of GPs agreed that it was possible to reduce or stop psychotropic drugs for these patients. Characteristics of 339 patients taking psychotropic drug were reported: 85.8% (291/339) received at least one anxiolytic/hypnotic and 56.9% (193/339) received at least one antidepressant; there were prescribed for more than 1 year in 68.4% (199/291) and 43.5% (84/193) of the cases respectively. GPs stated that it was possible to reduce or stop anxiolytic/hypnotic drugs for only 27% (79/291) of these patients. Barriers to doing this were patients' refusal (79%), and the absence of any local offer of psychotherapy (73%) or alternative therapy (70%). CONCLUSION: A mismatch exists between GPs' intent (91%) and practice (27%) regarding reduction of psychotropic prescription in individuals aged > or =65 years. The barriers encountered should be examined further to help physicians improve management of psychotropic prescription.

Estimating in real time the efficacy of measures to control emerging communicable diseases.

Controlling an emerging communicable disease requires prompt adoption of measures such as quarantine. Assessment of the efficacy of these measures must be rapid as well. In this paper, the authors present a framework to monitor the efficacy of control measures in real time. Bayesian estimation of the reproduction number R (mean number of cases generated by a single infectious person) during an outbreak allows them to judge rapidly whether the epidemic is under control (R < 1). Only counts and time of onset of symptoms, plus tracing information from a subset of cases, are required. Markov chain Monte Carlo and Monte Carlo sampling are used to infer the temporal pattern of R up to the last observation. The operating characteristics of the method are investigated in a simulation study of severe acute respiratory syndrome-like outbreaks. In this particular setting, control measures lacking efficacy (R > or = 1.1) could be detected after 2 weeks in at least 70% of the epidemics, with less than a 5% probability of a wrong conclusion. When control measures are efficacious (R = 0.5), this situation may be evidenced in 68% of the epidemics after 2 weeks and 92% of the epidemics after 3 weeks, with less than a 5% probability of a wrong conclusion.

Real-time estimates in early detection of SARS.

We propose a Bayesian statistical framework for estimating the reproduction number R early in an epidemic. This method allows for the yet-unrecorded secondary cases if the estimate is obtained before the epidemic has ended. We applied our approach to the severe acute respiratory syndrome (SARS) epidemic that started in February 2003 in Hong Kong. Temporal patterns of R estimated after 5, 10, and 20 days were similar. Ninety-five percent credible intervals narrowed when more data were available but stabilized after 10 days. Using simulation studies of SARS-like outbreaks, we have shown that the method may be used for early monitoring of the effect of control measures.