Using filled prescription sequences to rank antidepressants: A nationwide replication study.

Ranking antidepressants according to their acceptability (i.e., a combination of both efficacy and tolerability) in the general population may help choosing the best first-line medication. This study aimed to replicate the results of a proof-of-concept study ranking anti-depressants according to the proportion of filled prescription sequences consistent with a continuation of the first treatment versus those consistent with a change. We used a nationwide cohort from the French national health data system (SNDS) to support the use of this method as a widely available tool to rank antidepressant treatments in real life settings. About 1.2 million people were identified as new antidepressant users in the SNDS in 2011. The outcome was clinical acceptability as measured by the continuation/failure ratio over the six-month period following the introduction of the first-line treatment. Continuation was defined as at least two refills of the same treatment. Failure was defined as a psychiatric hospitalization, death or at least one filled prescription of another antidepressant, an antipsychotic medication, or a mood-stabilizer. Adjusted Odds Ratios (aOR) and 95% Confidence Interval (CI) were computed through multivariable binary logistic regressions. We ranked antidepressant medications according to clinical acceptability. Escitalopram again was the most acceptable option, and the five following antidepressants were the same as in the replication sample of the proof-of-concept study, in order Fluoxetine, Paroxetine, Sertraline, Citalopram and Venlafaxine with aOR (95% CI) for continuation ranging from 0.79 (0.77-0.81) to 0.66 (0.64-0.67). The present study provides evidence that filled prescription sequences is a widely available, robust and reproductible tool to rank antidepressant treatments in real life settings.

Acceptability of Second-Line Antidepressant Medications Using Filled Prescription Sequences in a Nationwide Cohort Study.

Background: Although about half of patients do not respond to a first-line antidepressant medication, there is no consensus on the best second-line option. The aim of this nationwide population-based study was to rank antidepressants according to their relative acceptability (ie, efficacy and tolerability) using filled prescription sequences after failure of first treatment.Methods: About 1.2 million people were identified as new antidepressant users in the French national health data system in 2011. The inclusion criterion was having at least 2 filled prescriptions of a second-line treatment after a filled prescription of a first-line treatment, resulting in 63,726 participants. The outcome was clinical acceptability as measured by the continuation/change ratio for second-line treatment. Continuation sequence was defined as at least 2 refills of the same treatment. Change sequence was defined as at least 1 filled prescription of another antidepressant. Adjusted odds ratios (aORs) were computed through multivariable binary logistic regressions.Results: Intraclass switch had a better acceptability than interclass switch (aOR [95% CI]: 1.23 [1.20-1.28]). According to the first-line treatment, intraclass switch remained more acceptable for selective serotonin reuptake inhibitors only (1.37 [1.31-1.42]). For α2 blockers and tricyclic agents, combination antidepressant therapy was the most acceptable second-line option (1.59 [1.27-2.01] and 2.53 [1.53-4.04], respectively), whereas for serotonin-norepinephrine reuptake inhibitors there was no significant difference between the strategies. For other antidepressants, intraclass switch had lower acceptability than interclass switch (0.70 [0.51-0.95]).Conclusions: Administrative claim databases may help with ranking acceptability of second-line treatments in real world settings and complement randomized controlled trials in informing clinicians about the most acceptable second-line options according to the first-line treatment.

The Economic Burden of Disease in France From the National Health Insurance Perspective: The Healthcare Expenditures and Conditions Mapping Used to Prepare the French Social Security Funding Act and the Public Health Act.

BACKGROUND: Identifying the most frequently treated and the costliest health conditions is essential for prioritizing actions to improve the resilience of health systems. OBJECTIVES: Healthcare Expenditures and Conditions Mapping describes the annual economic burden of 58 health conditions to prepare the French Social Security Funding Act and the Public Health Act. DESIGN: Annual cross-sectional study (2015-2019) based on the French national health database. SUBJECTS: National health insurance beneficiaries (97% of the French residents). MEASURES: All individual health care expenditures reimbursed by the national health insurance were attributed to 58 health conditions (treated diseases, chronic treatments, and episodes of care) identified by using algorithms based on available medical information (diagnosis coded during hospital stays, long-term diseases, and specific drugs). RESULTS: In 2019, €167.0 billion were reimbursed to 66.3 million people (52% women, median age: 42 y). The most prevalent treated diseases were diabetes (6.0%), chronic respiratory diseases (5.5%), and coronary diseases (3.2%). Coronary diseases accounted for 4.6% of expenditures, neurotic and mood disorders 3.7%, psychotic disorders 2.8%, and breast cancer 2.1%. Between 2015 and 2019, the expenditures increased primarily for diabetes (+€906 million) and neurotic and mood disorders (+€861 million) due to the growing number of patients. "Active lung cancer" (+€797 million) represented the highest relative increase (+54%) due to expenditures for the expensive drugs and medical devices delivered at hospital. CONCLUSIONS: These results have provided policy-makers, evaluators, and public health specialists with key insights into identifying health priorities and a better understanding of trends in health care expenditures in France.

Characteristics of people with severe hypertension in France and determinants of medication persistence after 6 years.

BACKGROUND: Low medication persistence is reported in patients with severe hypertension but few data are available according to drug classes. METHOD: Adults without cardiovascular disease who started treatment, in a semester between 2010 and 2012, with two concurrent dispensings of at least three classes were identified in the French national health data system. High persistence after 12 semesters of follow-up was defined by a 6-monthly mean of number of drug classes equal to or greater than 80%. RESULTS: Five hundred and seventy-six thousand and forty-eight adults alive at 6 years were included (three classes: 79%, four classes: 18%, five or more classes: 4%) with a mean age of 65.3 years, constituting 42% of men. High persistence was observed for 72% of people and multivariate analysis of baseline factors found a negative association for: female sex, extreme ages, living in an overseas department, at least one comorbidity, absence or frequent general practitioner consultations and a cardiologist consultation. The adjusted odds ratio was low for dispensing of ACEIs (0.87; 95% CI: 0.8-0.95), other RAS antagonists (0.91; 95% CI: 0.83-0.99) and a high number of classes (4: 0.17; 95% CI: 0.15-0.19, five and more: 0.06; 95% CI: 0.05-0.08). An inverse association was observed for diuretics (1.45; 95% CI: 1.33-1.59), calcium channel blockers (1.63; 95% CI: 1.50-1.79), beta-blockers (1.92; 95% CI: 1.76-2.1) and other antihypertensive classes (1.6; 95% CI: 1.5-1.8). No significant association was observed for ARBs (1.0; 95% CI: 0.9-1.1). CONCLUSION: These results based on a large primary prevention population should encourage the implementation of new pharmacological and nonpharmacological management strategies for people with severe hypertension in France.

Intensity of Care, Expenditure, and Place of Death in French Women in the Year Before Their Death From Breast Cancer: A Population-Based Study.

Health care utilization of women with breast cancer (BC) during the last year of life, together with the causes and place of death and associated expenditure have been poorly described. Women treated for BC (2014-2015) with BC as a cause of death in 2015 and covered by the national health insurance general scheme (77% of the population) were identified in the French health data system (n = 6,696, mean age: 68.7 years, SD ± 15). Almost 70% died in short-stay hospitals (SSH), 4% in hospital-at-home (HaH), 9% in Rehab, 5% in skilled nursing homes (SNH) and 12% at home. One-third presented cardiovascular comorbidity. During the last year, 90% were hospitalized at least once in SSH, 25% in Rehab, 13% in HaH and 71% received hospital palliative care (HPC), but only 5% prior to their end-of-life stay. During the last month, 85% of women were admitted at least once to a SSH, 42% via the emergency department, 10% to an ICU, 24% received inpatient chemotherapy and 18% received outpatient chemotherapy. Among the 83% of women who died in hospital, independent factors for HPC use were cardiovascular comorbidity (adjusted odds ratio, aOR: 0.83; 95%CI: 0.72-0.95) and, in the 30 days before death, at least one SNH stay (aOR: 0.52; 95%CI: 0.36-0.76), ICU stay (aOR: 0.36; 95%CI: 0.30-0.43), inpatient chemotherapy (aOR: 0.55; 95%CI: 0.48-0.63), outpatient chemotherapy (aOR: 0.60; 95%CI: 0.51-0.70), death in Rehab (aOR: 1.4; 95%CI: 1.05-1.86) or HAH (aOR: 4.5; 95%CI: 2.47-8.1) vs SSH. Overall mean expenditure reimbursed per woman was €38,734 and €42,209 for those with PC. Women with inpatient or outpatient chemotherapy during the last month had lower rates of HPC, suggesting declining use of HPC before death. This study also indicates SSH-centered management with increased use of HPC in HaH and Rehab units and decreased access to HPC in SNH.

Less amputations for diabetic foot ulcer from 2008 to 2014, hospital management improved but substantial progress is still possible: A French nationwide study.

OBJECTIVE: To assess the improvement in the management of diabetes and its complications based on the evolution of hospitalisation rates for diabetic foot ulcer (DFU) and lower extremity amputation (LEA) in individuals with diabetes in France. METHODS: Data were provided by the French national health insurance general scheme from 2008 to 2014. Hospitalisations for DFU and LEA were extracted from the SNIIRAM/SNDS French medical and administrative database. RESULTS: In 2014, 22,347 hospitalisations for DFU and 8,342 hospitalisations for LEA in patients with diabetes were recorded. Between 2008 and 2014, the standardised rate of hospitalisation for DFU raised from 508 to 701/100,000 patients with diabetes. In the same period, the standardised rate of LEA decreased from 301 to 262/100,000 patients with diabetes. The level of amputation tended to become more distal. The proportion of men (69% versus 73%) and the frequency of revascularization procedures (39% versus 46%) increased. In 2013, the one-year mortality rate was 23% after hospitalisation for DFU and 26% after hospitalisation for LEA. CONCLUSIONS: For the first time in France, the incidence of a serious complication of diabetes, i.e. amputations, has decreased in relation with a marked improvement in hospital management.

COVID-19-related complications and decompression illness share main features.: Could the SARS-CoV2-related complications rely on blood foaming?

A study by Saraiva et al. (2011) demonstrated the presence of Angiotensin II receptors on the erythrocyte membrane. This little-known information should be deemed as crucial as the SARS-CoV-2 relationships with oxygen saturation and the Renine Angiotensin System but it currently remains unexploited. The pulmonary and cardiovascular systems are involved in any typical complications of COVID-19 but numerous other unrelated symptoms may occur. To fill the gap, we shall first emphasize some similarities between the complications of this infectious disease and Decompression Illness (DCI), which involves bubble formation. We theorized that the Angiotensin II clearance by the red blood cells could trigger the release of its oxygen content in the bloodstream. The resulting foam would worsen the widespread endotheliitis, worsen the gas exchange, trigger the coagulation process, the inflammation process and the complement pathway as typically occurs in DCI. At the end, we propose a plausible mechanism.

Intensity of care, expenditure, place and cause of death people with lung cancer in the year before their death: A French population based study.

INTRODUCTION: Health care utilization of people with lung cancer (LC) the last year of life, their causes of death and place of death and the associated expenditure have been poorly described together. Then we conducted an observational study. METHODS: People with LC covered by the French health Insurance general scheme (77% of the population) who died in 2015 were identified in the national health data system, together with their health care utilization and, in 95% of cases, their causes of death. RESULTS: A total of 22,899 individuals were included (mean age: 68 years, SD±11.4), 72% of whom died in short-stay hospitals (SSH), 4% in hospital-at-home, 8% in Rehab hospital, 2% in skilled nursing homes and 14% at home. One-half of these people had also a chronic respiratory tract disease and 18% another cancer. Hospital palliative care (HPC) was identified for 65% of people, but for only 9% prior to their end-of-life stay. During the last month of life, 49% of people had two or more SSH stays, 15% were admitted to an intensive care unit, 23% received a chemotherapy session (13% during the last 14 days). The main cause of death was cancer for 92% of individuals (LC for 82%) The mean expenditure during the last year of life was €43,329 per individual. DISCUSSION: This study indicates high rates of intensive care unit admissions and chemotherapy during the last month of life and a SSH hospital-centered management with intensive use of HPC mainly during the end-of-life stay.

The economic burden of diabetes to French national health insurance: a new cost-of-illness method based on a combined medicalized and incremental approach.

A better understanding of the economic burden of diabetes constitutes a major public health challenge in order to design new ways to curb diabetes health care expenditure. The aim of this study was to develop a new cost-of-illness method in order to assess the specific and nonspecific costs of diabetes from a public payer perspective. Using medical and administrative data from the major French national health insurance system covering about 59 million individuals in 2012, we identified people with diabetes and then estimated the economic burden of diabetes. Various methods were used: (a) global cost of patients with diabetes, (b) cost of treatment directly related to diabetes (i.e., 'medicalized approach'), (c) incremental regression-based approach, (d) incremental matched-control approach, and (e) a novel combination of the 'medicalized approach' and the 'incremental matched-control' approach. We identified 3 million individuals with diabetes (5% of the population). The total expenditure of this population amounted to €19 billion, representing 15% of total expenditure reimbursed to the entire population. Of the total expenditure, €10 billion (52%) was considered to be attributable to diabetes care: €2.3 billion (23% of €10 billion) was directly attributable, and €7.7 billion was attributable to additional reimbursed expenditure indirectly related to diabetes (77%). Inpatient care represented the major part of the expenditure attributable to diabetes care (22%) together with drugs (20%) and medical auxiliaries (15%). Antidiabetic drugs represented an expenditure of about €1.1 billion, accounting for 49% of all diabetes-specific expenditure. This study shows the economic impact of the assumption concerning definition of costs on evaluation of the economic burden of diabetes. The proposed new cost-of-illness method provides specific insight for policy-makers to enhance diabetes management and assess the opportunity costs of diabetes complications' management programs.

[Epidemiology of type 1 diabetes and its complications]. / Épidémiologie du diabète de type 1 et de ses complications.

Epidemiology of type 1 diabetes and its complications. The prevalence of type 1 diabetes in adult is estimated at 0.3 to 0.5%, or 10% of all types of diabetes. In youth less than 15 years, in France, the incidence of type 1 diabetes is 18 per 100,000 over the period 2013-2015 (based on the National Health Data System), corresponding to an approximate prevalence of 1.3 per 1000. The incidence of diabetes in youth increases by 3 to 4% per year, an increase seen in France since 1988. With the intensification of treatment (resulting in HbA1c around 8% on average over the entire follow-up), after 30 years of progression of diabetes (in subjects aged 50 years on average), it was observed that the prevalence of severe retinopathy (requiring laser treatment) was nearly 15%, microalbuminuria 15%, macroproteinuria 4%, advanced renal failure less than 2%, clinical neuropathy 24%, and macrovascular complications around 5%.

Épidémiologie du diabète et de ses complications. La prévalence du diabète de type 1 chez l'adulte est estimée entre 0,3 à 0,5 %, soit 10 % de l'ensemble des diabètes. Chez les moins de 15 ans, en France, l'incidence du diabète de type 1 est de 18 pour 100 000 sur la période 2013-2015 (à partir du système national des données de santé), correspondant à une prévalence de l'ordre de 1,3 pour 1 000. L'incidence du diabète du sujet jeune augmente de 3 à 4 % par an, augmentation repérée en France depuis l'année 1988. Avec l'intensification du traitement (aboutissant à une hémoglobine glyquée autour de 8 % en moyenne sur l'ensemble du suivi), après 30 ans d'évolution du diabète (chez des sujets âgés de 50 ans en moyenne), il a été observé une fréquence de rétinopathie sévère (nécessitant un traitement par laser) de près de 15 %, de microalbuminurie de 15 %, de macroprotéinurie de 4 %, d'insuffisance rénale avancée de moins de 2 %, de neuropathie clinique de 24 %, et de complications macrovasculaires de l'ordre de 5 %.

[The human and economic burden of cancer in France in 2014, based on the Sniiram national database]. / Poids humain et économique des cancers en France en 2014, les données du Sniiram.

INTRODUCTION: The national health insurance information system (Sniiram) can be used to estimate the national medical and economic burden of cancer. This study reports the annual rates, characteristics and expenditure of people reimbursed for cancer. METHODS: Among 57 million general health scheme beneficiaries (86% of the French population), people managed for cancer were identified using algorithms based on hospital diagnoses and full refund for long-term cancer. The reimbursed costs (euros) related to the cancer, paid off by the health insurance, were estimated. RESULTS: In 2014, 2.491 million people (4.4%) covered by the general health scheme had a cancer managed (men 1.1 million, 5.1%; women 1.3 million, 4.9%). The annual (2012-2014) average growth rate of patients was 0.8%. The spending related to the cancer was 13.5 billion: 5 billion for primary health care (drugs 2.3 billion), 7.5 billion for the hospital (drugs 1.3 billions) and 900 million for sick leave and invalidity pensions. Spending annual average growth rate (2012-2014) was 4% (drugs 2%). The rates of patients and the relative spending were 1.8% and 2.5 billion for the breast cancer (women), 1.5% and 1.0 billion for prostate cancer, 0.9% and 1.5 billion for the colon cancer, and 0.19% and 1.3 billion for lung cancer. DISCUSSION: Cancers establish one of the first groups of chronic diseases pathologies in terms of patients and spending. If the numbers of patients remain stables, the spending increases, mainly for medicines.

Prevalence and economic burden of cardiovascular diseases in France in 2013 according to the national health insurance scheme database.

BACKGROUND: Cardiovascular diseases (CVDs) constitute the second leading cause of death in France. The Système national d'information interrégimes de l'assurance maladie (SNIIRAM; national health insurance information system) can be used to estimate the national medical and economic burden of CVDs. OBJECTIVES: To describe the rates, characteristics and expenditure of people reimbursed for CVDs in 2013. METHODS: Among 57 million general health scheme beneficiaries (86% of the French population), people managed for CVDs were identified using algorithms based on hospital diagnoses either during the current year (acute phase) or over the previous 5 years (chronic phase) and long-term diseases. The reimbursed costs attributable to CVDs were estimated. RESULTS: A total of 3.5 million people (mean age, 71 years; 42% women) were reimbursed by the general health scheme for CVDs (standardized rate, 6.5%; coronary heart disease, 2.7%; arrhythmias/conduction disorders, 2.1%; stroke, 1.1%; heart failure, 1.1%). These frequencies increased with age and social deprivation, and were higher in Northern and Eastern France and Réunion Island. The total sum reimbursed by all schemes for CVDs was € 15.1 billion (50% for hospital care and 43% for outpatient care [including 15% for drugs and 12% for nurses/physiotherapists]); coronary heart disease accounted for € 4 billion, stroke for € 3.5 billion and heart failure for € 2.5 billion (i.e. 10% of the total expenditure reimbursed by all national health insurance schemes for all conditions). CONCLUSION: CVDs constitute the leading group in terms of numbers of patients reimbursed and total reimbursed expenditure, despite a probable underestimation of both numbers and expenditure.

Impact of Perceived Stress, Anxiety-Depression and Social Support on Coping Strategies of Parents Having A Child With Gilles de la Tourette Syndrome.

PURPOSE: Previous reports have indicated that raising a child with Gilles de la Tourette syndrome (GTS) could be considered a stressful experience. Thus our study aimed to assess the impact of perceived stress (i.e. parental cognitive perception of their child's disorder) and social support (number of people surrounding the subject providing support) on coping strategies-defined as processes of restoring balance between excessive demands and inadequate resources-of parents having a child with GTS. METHODS: Twenty-eight parents of 21 patients with GTS (aged 6 to 16years) completed questionnaires on perceived stress (ALE Scale), social support (SSQ6), coping strategies (WCC-R) and anxiety-depression (HAD). RESULTS: Principal component analysis showed a negative correlation between social support on one side and perceived stress and anxiety/depression on the other. Problem- and emotion-focused coping both correlated with social support, all of them being independent from perceived stress and anxiety/depression. Hierarchical ascendant classification showed three clusters of individuals in our parents' groups: i) those having high scores in perceived stress and anxiety-depression; ii) those having high scores in social support associated with low scores in perceived stress; iii) parents having lower than average scores on both problem- and emotion- focused coping and social support. CONCLUSION: Our results reinforce the need for developing training programs for parents with GTS children to better understand and tolerate the disorder to decrease their stress.

Heuristic consequences of a load of oxygen in microtubules.

The current cell oxygen paradigm shows some major gaps that have not yet been resolved. Something seems to be lacking for the comprehensive statement of the oxygen distribution in the cell, especially the low cytoplasmic oxygen level. The entrapment of oxygen in microtubules (MTs) resolves the latter observation, as well as the occurrence of an extensive cytoplasmic foam formation. It leads to a novel oxygen paradigm for cells. During the steady-state treadmilling, the mobile cavity would absorb oxygenated cytoplasm forward, entrap gas nuclei and concentrate them. A fluorescence method is described to confirm the in vitro load of oxygen in MTs during their periodic growths and shrinkages. The latter operating mechanism is called the gas dynamic instability (GDI) of MTs. Several known biosystems could rest on the GDI. (1) The GTP-cap is linked with the gas meniscus encountered in a tube filled with gas. The GTP hydrolysis is linked to the conformational change of the GTPase domain according to the bubble pressure, and to the shaking of protofilaments with gas particles (soliton-like waves). (2) The GDI provides a free energy water pump because water molecules have to escape from MT pores when foam concentrates within the MT. Beside ATP hydrolysis in motor proteins, the GDI provides an additional driving force in intracellular transport of cargo. The water streams flowing from the MT through slits organize themselves as water layers between the cargo and the MT surface, and break ionic bridges. It makes the cargo glide over a water rail. (3) The GDI provides a universal motor for chromosome segregation because the depolymerization of kinetochorial MTs is expected to generate a strong cytoplasmic foam. Chromosomes are sucked up according to the pressure difference (or density difference) applied to opposite sides of the kinetochore, which is in agreement with Archimedes' principle of buoyancy. Non-kinetochorial MTs reabsorb foam during GDI. Last, the mitotic spindle is imagined as a gas recycler. (4) The luminal particles within MTs (called MIPs) are imagined as a foam organizer, the luminal proteins being part of the borders and edges of identical bubbles. (5) Last, volatile anesthetics could destabilize MTs through anesthetic-induced bubble nucleation between protofilaments, and therefore causing shear stress and the opening of MT. The load of oxygen in MTs might provide a major advance in this area of research.

Alzheimer's disease: a gas model. The NADPH oxidase-Nitric Oxide system as an antibubble biomachinery.

Alzheimer's disease (AD) is a neurodegenerative disease of unknown origin. The pathological lesions that define AD would be linked to the insidious accumulation of nitrogen, having invaded the brain interstitial fluid (ISF) from the blood via the physiological cycling pool of vascular glucose transporters (GLUT-1). According to this hypothesis, the nitrogen nanobubbles, being chemically inert and actually indestructible for human beings, can not escape from the ISF anymore. They would exert a huge and deleterious pressure against cellular components, especially in microglia and in astrocytes. They could enhance the existing cell oxygen anisotropy, which might enhance the natural bubble nucleation of O2-2O2 in cells or in mitochondria. Indeed, with the help of a new symbolic representation for gas nuclei in chemical reactions, the NADPH oxidase-NO system is identified for the first time, as an antibubble biomachinery, able to break O2-2O2 bubbles up as it releases superoxide O2-. Superoxide is considered as a quantum bubble, which collapses through the reactivity of the gaseous NO radical. Their combination in soluble peroxinitrite provides the change from one state of matter to another, avoiding any risk of a bubble enlargement, and finally avoiding the risk of enzyme crowding or of a bulk pressure variation. However, a bubble is expected to entrap Nitric Oxide (NO), which leads theoretically to a decrease in its bioavailability, and is expected to trigger a guanylyl-cyclase-mediated inflammatory cascade, that could explain the inflammation in AD. In vitro, any increase in the hydrostatic pressure has already been linked to the microtubule disorganization. The amyloid deposits, also known as senile plaques, would behave as a sponge toward ISF nitrogen; Aß is considered as a foam-stabilizing agent. By taking the shape of cerebral amyloid angiopathy, the amyloid could confine the nitrogen leak from the blood, and progressively insulate the Blood-Brain Barrier against the pollutant. All these theoretical features finally lead to the death of the neurons. The comprehensive statement of the theoretical pro-inflammatory action of inert gases is a real upheaval for the whole medicine.

Analytical performance of several classical swine fever laboratory diagnostic techniques on live animals for detection of infection.

The diagnostic properties of several assays on live animals were studied using data from different experiments. These experiments involved 128 classical swine fever virus (CSFV) infected pigs (weaner pigs, fatteners and sows). Since all pigs in the study were infected with CSFV, only the proportion of test positive results and the time until a test positive result is obtained were evaluated. The RT-nPCR detected the highest proportion of infected pigs (98.9%), whereas the Antigen ELISA gave the worst detection results (74.7%). Within the group of test positive animals, infection was detected earliest using the leukocyte count and latest using Antigen ELISA. Using the virus neutralisation test, antibodies against CSFV were detectable on average 7.6 days after the onset of viraemia in virus isolation in whole blood. Using survival analysis, the time until the first positive diagnosis and the proportion of detected animals were combined in one test. Results showed that RT-nPCR performed significantly better than either virus isolation in different blood fractions or antigen ELISA. It is concluded that the RT-nPCR technique is the best diagnostic tool available for early detection of a classical swine fever infection.