Estimating the number of probable new SARS-CoV-2 infections among tested subjects from the number of confirmed cases.

OBJECTIVES: In most African countries, confirmed COVID-19 case counts underestimate the number of new SARS-CoV-2 infection cases. We propose a multiplying factor to approximate the number of biologically probable new infections from the number of confirmed cases. METHODS: Each of the first thousand suspect (or alert) cases recorded in South Kivu (DRC) between 29 March and 29 November 2020 underwent a RT-PCR test and an IgM and IgG serology. A latent class model and a Bayesian inference method were used to estimate (i) the incidence proportion of SARS-CoV-2 infection using RT-PCR and IgM test results, (ii) the prevalence using RT-PCR, IgM and IgG test results; and, (iii) the multiplying factor (ratio of the incidence proportion on the proportion of confirmed -RT-PCR+- cases). RESULTS: Among 933 alert cases with complete data, 218 (23%) were RT-PCR+; 434 (47%) IgM+; 464 (~ 50%) RT-PCR+, IgM+, or both; and 647 (69%) either IgG + or IgM+. The incidence proportion of SARS-CoV-2 infection was estimated at 58% (95% credibility interval: 51.8-64), its prevalence at 72.83% (65.68-77.89), and the multiplying factor at 2.42 (1.95-3.01). CONCLUSIONS: In monitoring the pandemic dynamics, the number of biologically probable cases is also useful. The multiplying factor helps approximating it.

Improving survival in end-stage renal disease: A case study.

Background: With the increase of life expectancy, *On behalf of the REIN registry. end-stage renal disease (ESRD) is affecting a growing number of people. Simultaneously, renal replacement therapies (RRTs) have considerably improved patient survival. We investigated the way current RRT practices would affect patients' survival. Methods: We used a multi-state model to represent the transitions between RRTs and the transition to death. The concept of "crude probability of death" combined with this model allowed estimating the proportions of ESRD-related and ESRD-unrelated deaths. Estimating the ESRD-related death rate requires comparing the mortality rate between ESRD patients and the general population. Predicting patients' courses through RRTs and Death states could be obtained by solving a system of Kolmogorov differential equations. The impact of practice on patient survival was quantified using the restricted mean survival time (RMST) which was compared with that of healthy subjects with same characteristics. Results: The crude probability of ESRD-unrelated death was nearly zero in the youngest patients (18-45 years) but was a sizeable part of deaths in the oldest (≥70 years). Moreover, in the oldest patients, the proportion of expected death was higher in patient without vs. with diabetes because the former live older. In men aged 75 years at first RRT, the predicted RMSTs in patients with and without diabetes were, respectively, 61% and 69% those of comparable healthy men. Conclusion: Using the concept of "crude probability of death" with multi-state models is feasible and useful to assess the relative benefits of various treatments in ESRD and help patient long-term management.

Evolution of the incidence of hepatitis B virus infection and immunization rates in a large French cohort born between 1960 and 1994.

In France, several successive changes in anti-hepatitis B virus (HBV) vaccination policies occurred since 1982. We estimated the incidence and prevalence of HBV infection according to years of birth 1960 to 1994 in a large sentinel cohort to evaluate the epidemiology of HBV during vaccination policy changes. A retrospective cohort study included data from all HIV, HBV and hepatitis C virus (HCV) screening facilities in Grand Lyon. From 2005 to 2010, all 57113 individuals with complete HBV serologic status were enrolled. Survival analyses modeled separately various ages in each birth cohort. The proportion of immunized individuals increased in birth cohorts 1978 to 1984 (up to 58.3% (95% confidence interval (CI), 43.3-68.2 at age 15). In post-1985 birth cohorts, this proportion decreased to 19.5% (95% CI, 15.5-24) in birth cohort 1987 at age 15. Probability of past or current HBV infection increased constantly in birth cohorts 1960 to 1967, up to 12% (95% CI, 10.4-14) at age 30, then decreased gradually in birth cohorts 1968 to 1991, down to 0.9% (95% CI, 0.7-1.2) at age 17.5. In post-1991 cohorts, the probability of HBV infection increased again, up to 2.5% (95% CI, 1.7-3.6) at age 17.5. HBV incidence fluctuated between 5 and 8 per 1000 person-years in pre-1986 birth cohorts, decreased to 2.1 (95% CI, 1.5-2.7) in birth cohorts 1986 to 1991 but rebounded to 5 (95% CI, 3.5-7.1) in post-1991 birth cohorts. HBV incidence was remarkably high in young adults with noticeable variations concomitantly to vaccination policy changes. A dramatic decline in immunization rate was temporally associated with a sharp rebound of infection after withdrawal of systematic adolescent vaccination in 1998.

Systemic lupus erythematosus-associated acute transverse myelitis: manifestations, treatments, outcomes, and prognostic factors in 20 patients.

BACKGROUND: Transverse myelitis is a rare complication of systemic lupus erythematosus (SLE). This retrospective multicentre study identifies the prognostic factors in a relatively large patient series. PATIENTS AND METHODS: Twenty patients fulfilled the SLE criteria of the ACR classification and the Transverse Myelitis Consortium Working Group. A severe neurological flare was defined as muscle strength grade <3/5 in more than half the muscle groups at the motor neurological level. Inability to run or another significant ambulation-unrelated disability was considered as 'unfavourable neurological outcome'. RESULTS: Myelitis was the first SLE symptom in 12 patients; in the eight others, it occurred 8.6 years (median delay) after SLE onset. Eleven patients presented severe neurological impairments. The treatment included corticosteroids in all patients associated with intravenous cyclophosphamide in 11 and/or hydroxychloroquine in 14. Unfavourable outcomes were observed in 53% of the patients at six months and in 28% at end of follow-up (median: 5.9 years). An initial severe neurological impairment and no cyclophosphamide use were associated with unfavourable neurological outcomes at six months and at end of follow-up, respectively. CONCLUSION: Transverse myelitis may reveal SLE or occur more than 10 years after SLE diagnosis. The initial severity of the neurological flare (with paraplegia) is the main prognostic marker. The study provides arguments for cyclophosphamide use.

National cancer incidence is estimated using the incidence/mortality ratio in countries with local incidence data: is this estimation correct?

BACKGROUND: In countries with local cancer registration, the national cancer incidence is usually estimated by multiplying the national mortality by the incidence/mortality (I/M) ratio from pooled registries. This study aims at validating this I/M estimation in France, by a comparison with estimation obtained using the ratio of incidence over hospital discharge (I/HD) or the ratio of incidence over health insurance data (long-duration diseases, I/LDD). METHODS: This comparison was performed for 22 cancer sites over the period 2004-2006. In France, a longitudinal I/M approach was developed relying on incidence and mortality trend analyses; here, the corresponding estimations of national incidence were extracted for 2004-2006. The I/HD and I/LDD estimations were performed using a common cross-sectional methodology. RESULTS: The three estimations were found similar for most cancers. The relative differences in incidence rates (vs. I/M) were below 5% for numerous cancers and below 10% for all cancers but three. The highest differences were observed for thyroid cancer (up to +21% in women and +8% in men), skin melanoma (up to +13% in women and +8% in men), and Hodgkin disease in men (up to +15%). Differences were also observed in women aged over 60 for cervical cancer. Except for thyroid cancer, differences were mainly due to the smoothing performed in the I/M approach. CONCLUSION: Our results support the validity of I/M approaches for national estimations, except for thyroid cancer. The longitudinal version of this approach has, furthermore, the advantage of providing smoothed estimations and trend analyses, including useful birth-cohort indicators, and should thus be preferred.

[Diversity of incidence trend patterns: implications for carcinogenesis?]. / Diversité des modèles d'évolution des incidences: implication en cancérogenèse?

OBJECTIVE: Cancers of the ENT, oesophagus and lungs are caused mainly by alcohol and/or tobacco consumption but have potentially heterogeneous latencies and dose-incidence relationships. The incidence of cancers having the same risk factors may vary in a similar way over time and space. The aim of the study was to identify groups of cancers with similar spatio-temporal incidence trends. METHODS: Fifty thousand nine hundred and eighty cases of ten cancer types were collected between 1982 and 2002 in six French departments. The incidence levels and trends were assessed using an age-cohort random-effect model that took into account heterogeneity of incidence levels and trends between departments. RESULTS: Three groups of cancer sites/types with similar spatio-temporal incidence trends were identified: (1) oral cavity, oropharynx, hypopharynx, larynx, oesophagus, and lung squamous cell carcinomas in which the incidence decreased similarly in time and space; (2) other types of lung cancer and lung adenocarcinomas whose incidence increased similarly; and (3) lung large- and small-cell carcinomas whose incidence trends were heterogeneous. CONCLUSION: Using the tools of descriptive epidemiology different cancer groups with different temporal and spatial incidence trends were identified. This diversity suggests different latencies and different sensitivities of those groups to the main risk factors, alcohol and tobacco.

Long-term outcomes of chronic minimally conscious and vegetative states.

OBJECTIVE: The present retrospective cohort study compares the long-term functional outcome, improvement or deterioration, of patients considered in a vegetative state (VS) or a minimally conscious state (MCS) 1 year after coma onset, then yearly for up to 5 years. METHODS: We reviewed the clinical courses of 12 patients in VS and 39 in MCS. The outcomes were assessed at 2, 3, 4, and 5 years after injury using the 5 categories of the Glasgow Outcome Scale plus an additional category for patients in MCS. A logistic regression analysis investigated the relationships between each outcome and 10 predictor variables. Four of these variables were auditory evoked potentials recorded at the early stage of coma. RESULTS: None of the patients in VS improved during the follow-up period: 1 was lost to follow-up, 9 died, and 2 remained in VS. Among patients in MCS, 3 were lost to follow-up, 14 died, 9 remained in MCS, and 13 emerged from MCS with severe disabilities. VS, age >39 years, and bilateral absence of cortical components of middle-latency auditory evoked potentials were significantly associated with deterioration. CONCLUSIONS: In contrast to patients in VS, a third of patients in MCS improved more than 1 year after coma onset. This emphasizes the need to define reliable boundaries between VS and MCS using repeated clinical evaluations and all imaging and neurophysiologic tools available today.

Is it possible to estimate the incidence of breast cancer from medico-administrative databases?

One approach to estimate cancer incidence in the French Départements is to quantify the relationship between data in cancer registries and data obtained from the PMSI (Programme de Médicalisation des Systèmes d'Information Médicale). This relationship may then be used in Départements without registries to infer the incidence from local PMSI data. We present here some methodological solutions to apply this approach. Data on invasive breast cancer for 2002 were obtained from 12 Départemental registries. The number of hospital stays was obtained from the National PMSI using two different algorithms based on the main diagnosis only (Algorithm 1) or on that diagnosis associated to a mention of "resection" (Algorithm 2). Considering registry data as gold standard, a calibration approach was used to model the ratio of the number of hospital stays to the number of incident cases. In Départements with registries, validation of the predictions was done through cross-validation. In Départements without registries, validation was done through a study of homogeneity of the mean number of hospital stays per patient. Cross-validation showed that the estimates predicted by the model were true with data extracted by Algorithm 1 but not by Algorithm 2. However, with Algorithm 1, there was an important heterogeneity between French Départements as to the mean number of hospital stays per patient, which had an important impact on the estimations. In the near future, the method will allow using medico-administrative data (after calibration with registry data) to estimate Départemental incidence of selected cancers.

Plasma fatty acids and lipid hydroperoxides increase after antibiotic therapy in cystic fibrosis.

The present authors investigated whether cystic fibrosis is linked to a defect in fatty acids and assessed the impact of the main patients' characteristics on the levels of several fatty acids, mostly during respiratory exacerbation and after antibiotic therapy. Fatty acid phospholipid and cholesteryl ester levels were measured in stable-state patients and controls. No differences were found concerning either the fractions of palmitic and oleic acids or the cholesteryl esters of alpha-linolenic and arachidonic acids. However, phospholipids of alpha-linolenic and arachidonic acids, as well as cholesteryl esters and phospholipids of stearic and linoleic acids, were lower in patients than in controls, but fractions of dihomo-gamma-linolenic, docosatetraenoic, docosapentaenoic, palmitoleic and eicosatrienoic acids were higher. Fatty acid levels, oxidative stress markers, nutrients, body mass index and forced expiratory volume in one second (FEV(1)) were measured in patients before and after antibiotic courses for bronchial exacerbation. After adjustments, palmitic, stearic, alpha-linolenic, linoleic, arachidonic, palmitoleic and oleic acids generally decreased during exacerbation but almost all increased after antibiotic courses. Nearly all fractions increased along with FEV(1) and a positive relationship linked fatty acids to lipid hydroperoxides. There was no general drop in fatty acids. Patients' fatty acid profiles depended on the pulmonary function and the inflammation state.

Modelling the progression towards duodenal cancer among patients with familial polyposis on the basis of two different score profiles.

The objective was to design a method that considers, on clinical arguments, the likely existence of patient subgroups with different evolution profiles. The method is applied in familial adenomatous polyposis to predict the proportion of patients that would develop duodenal cancer. A subject-specific linear mixed-effects model was elaborated to explicitly model heterogeneity in regression parameters. The estimates of the parameters were obtained by Bayesian inference using Gibbs sampling. The application concerned two potential polyposis subgroups: stable-state and progressive. Each patient's score was expressed in function of his putative subgroup, the reference subgroup mean score (intercept), the rate of change (slope), and time. The estimated proportion of stable-state patients was 35%. In progressive-state patients, the estimated annual score increase was 0.38 (95% CI: 0.27-0.48). The regression model predicted that the proportion of patients with a score > or = 9 is near 43% at age 60 (36-50%) and 50% at 70 (43-57%). The method indicates the evolution profile of each subject, which facilitates therapeutic decisions. The modelling may be extended to other more complex situations with several subgroups, with different change rates, or with various genetic or therapeutic profiles.

A new vacuum device as alternative treatment for impotence.

Vacuum erection devices are an acceptable alternative for the management of erectile dysfunction. The safety of such devices has been questioned because of their effects on penile blood flow. We report the use of Doppler ultrasonography to assess arterial flow and its value in ensuring long-term safety of a new external vacuum device. Sixteen patients were studied. At 3 months it was possible to confirm the efficacy and safety of the method and model in 14 patients, 12 of whom had a significant improvement in their sexual function. By 10 months, only 6 were continuing to use the device. Doppler sonography appears to be an effective technique for assessing penile blood flow during restriction from a vacuum device. The new vacuum device provides a satisfactory short-term alternative to other more invasive forms of therapy.

[The physiology of penile rigidity]. / Considérations sur la physiologie de la rigidité pénienne.

Penile tumescence and rigidity are considered to be a purely vascular process related to an increased inflow and a decreased outflow. This theory, which provides a satisfactory explanation for tumescence, is unable to explain the existence of high intracavernous pressures recorded both in animals and in man. Based on a hydrostatic model, the authors distinguish two phases involving different physiological mechanisms: an infrasystolic vascular phase and a suprasystolic muscular phase. During the vascular phase, the intracavernous pressure (ICP) can never exceed the systolic blood pressure. However, during the muscular phase, the ICP largely exceeds the systolic pressure, reaching values as high as 400 mmHg in man and 1,000 mmHg in animals. These variations in ICP can be explained by the contraction of perineal muscles, particularly the ischiocavernosus muscles. Various animal and human experiments are presented in support of this hypothesis. The pressure variations exerted on the glans during coitus by the perivaginal musculature are sufficient to induce reflex contractions of the ischiocavernosus muscles, promoting penile rigidity.

Elevation of cyclic adenosine monophosphate levels independently down regulates IL-1, IL-2, and IL-2 receptor (CD25) syntheses.

In view of the central involvement of interleukin-1 (IL-1) in T-cell functions and the negative effects exerted by cyclic adenosine monophosphate (cAMP) on T-cell responses, we wondered whether these inhibitions rely on defects in IL-1 generation. We investigated the effect of a known cAMP elevating agent, cholera toxin (CT), on the generation of IL-1 from peripheral blood adherent cells as well as the role of IL-1 whenever IL-2 synthesis and IL-2 receptor (CD25 antigen) expression are inhibited. While augmenting intracellular cAMP concentration, CT inhibits from 20 to 40% the generation of IL-1 activity from E. coli lipopolysaccharide (LPS)-stimulated adherent cells. Theophylline (TH), a cAMP degradation blocking agent, induces the same decrease in IL-1 activity. The B chain of CT, devoid of cAMP activating potency, is not inhibitory. In systems where CT and TH dramatically inhibit the generation of IL-2 activity (80%), addition of exogenous IL-1 does not restore the ability of T-cells to produce or release IL-2. Moreover, CT- and dibutyryl (db)cAMP-induced inhibition of CD25 antigen expression is not overcome by exogenous IL-1, IL-2, nor by both interleukins. It is concluded that inhibition of IL-1 and IL-2 production are independent and that inhibition of CD25 antigen expression is independent of IL-1 and IL-2 modulation. Cholera toxin and cAMP influences on interleukin synthesis are discussed.

Elevation of 3'5' cyclic adenosine monophosphate alters CD3 and CD25 antigens expression in activated T lymphocytes.

Modulation of CD3 molecules and expression of receptors for IL-2 (CD25) are pivotal events of lymphocyte activation and proliferation. Knowing the inhibitory effect of cAMP elevating agents on T lymphocyte activation, we investigated the effect of cholera toxin (CT) and dibutyryl cyclic AMP (dbcAMP) on the modulation of the CD3/Ti complex and on the appearance of the CD25 antigen on PHA-activated human lymphocytes. Cytofluorometry analysis of indirectly anti-CD3 labelled cells showed that CT accelerated the disappearance of CD3 molecules and slowed their reappearance. CT or dbcAMP inhibited the expression of CD25 antigen. In both cases, not only the relative number of CD3+ or CD25+ cells decreased, but the number of CD3 or CD25 antigens per cell as well. Exogenous rIL-2 did not reverse the inhibition of IL-2R expression by CT, showing that this effect is independent of the inhibition of IL-2 production already demonstrated. We conclude that augmenting cAMP levels might affect early steps of activation such as antigen receptor modulation, but do affect more profoundly late IL-2 dependent steps especially the autocrine IL-2 pathway of IL-2 receptor upregulation and the production of IL-2.

Elevation of cyclic 3'5' adenosine monophosphate levels by cholera toxin inhibits the generation of interleukin 2 activity.

Several molecules can interact with membrane receptors on mononuclear cells to increase intracellular levels of cyclic adenosine monophosphate (cAMP). We used the cholera toxin (CT), a cAMP elevating agent, to study the influence of this nucleotide on the production of interleukin 2 (IL-2) by human peripheral blood mononuclear cells stimulated by phytohemagglutinin and phorbol myristate acetate. Stimulated generation of IL-2 activity was inhibited by CT but not by its B subunit. The inhibition was potentiated by addition of theophylline. Therefore the synthesis and/or release of IL-2 is controlled by intracellular cAMP levels and may be modulated by agents active on this nucleotide system, such as bacterial toxins, glycoprotein hormones, or neurotransmitters.