Symptomatic Efficacy of Pharmacological Treatments for Knee Osteoarthritis: A Systematic Review and a Network Meta-Analysis with a 6-Month Time Horizon.

INTRODUCTION: Several pharmacological treatments aiming at a better symptomatic control of osteoarthritis (OA) are used in daily practice but their efficacy is often disputed. The purpose of this network meta-analysis (NMA) is to assess the efficacy on pain and function of the drugs that are most widely prescribed against knee OA. METHODS: Medline, Scopus, and Cochrane database of systematic reviews were searched for randomized controlled trials published up to August 2019 and assessing the efficacy of knee OA treatments using a 6-month time horizon. Pain and function changes from baseline were the primary outcomes. A Bayesian network meta-analysis was run and standardized mean differences (SMDs) with 95% credibility intervals (95% CrIs) were calculated. RESULTS: 9697 references were identified and 80 RCTs were concordant with our inclusion criteria (79 studies involving 15,609 individuals reported pain outcomes and 55 studies involving 13,655 individuals reported function outcomes). A significant decrease in pain was observed for the intra-articular (IA) combination of hyaluronic acid (HA) and triamcinolone (SMD - 0.49, 95% CrI - 0.78; - 0.19), vitamin D (SMD - 0.31, 95% CrI - 0.56; - 0.06), IA HA (SMD - 0.29, 95% CrI - 0.40; - 0.17), prescription-grade crystalline glucosamine sulfate (pCGS) (SMD - 0.29, 95% CrI - 0.58; - 0.004), and prescription-grade chondroitin sulfate (pCS) (SMD - 0.26, 95% CrI - 0.44; - 0.08). Significant improvements in physical function were found with pCGS (SMD - 0.44, 95% CrI - 0.66; - 0.21), vitamin D (SMD - 0.30, 95% CrIs - 0.49; - 0.11) and IA HA (SMD - 0.21, 95% CrIs - 0.31; - 0.11). CONCLUSION: Six months of treatment with IA HA, pCGS, pCS, vitamin D and the combination of IA HA and triamcinolone improve pain and/or physical function in patients suffering from knee OA.

Assessing the burden of Clostridium difficile infections for hospitals.

BACKGROUND: Nosocomial infections place a heavy burden on the healthcare system. However, quantifying the burden raises many questions, ranging from the way to accurately estimate the extra length of stay at hospital to defining and costing the preventive methods among the different care providers. AIM: To estimate the cost of nosocomial infection by C. difficile to inform the hospital managers. METHODS: Multi-state modelling based on Markov processes and bootstrapping was used to derive individual estimates of the prolongation of stay at hospital associated with Clostridium difficile infection (CDI). Indicators of cost for hospitals were then computed, including an estimation of the productivity losses derived from diagnosis-related group (DRG)-based payment systems. Patients were aged ≥55 years, admitted in two hospital facilities in Lille, with and without an episode of CDI from January 1st, 2013 to September 15th, 2014. FINDINGS: A total of 52 episodes were screened during the study period. The estimated mean cost of CDI was approximately €23,909 (SD: 17,458) for an extended length of hospital stay (N = 27). In the case of a reduced length of hospital stay (N = 25), the mean cost was approximately €-14,697 (SD: 16,936), which represents net savings for the hospitals. The main cost/savings driver was the productivity losses/gains resulting from the nosocomial infection. A sensitivity analysis showed that the main factor explaining the amount of costs or savings due to nosocomial infections was the length of the hospital stay. CONCLUSION: The notion of productivity gains in the case of deaths as a factor revealing the incompleteness of the payment systems is discussed, followed by the methodological issues associated with the statistical method used to control for temporality bias.

Coping with menopausal symptoms: An internet survey of Belgian postmenopausal women.

OBJECTIVES: An internet survey was performed to obtain data on the current use in Belgium of hormone replacement therapy and alternative treatments for the alleviation of menopausal symptoms. A supplementary aim was to assess the use of opt-in internet opinion panels (TalkToChange, http://www.talktochange.com, and GMI, http://www.gmi-mr.com/global-panel) as a potential new way to obtain data on menopausal issues. STUDY DESIGN: Data were collected via an internet platform from 696 postmenopausal women aged 45-60 years. OUTCOME MEASURES: Respondents were asked questions about their socio-demographic profile, their experience of the menopause, the burden of the menopause, its impact on their quality of life and the treatment of menopausal symptoms (if any). RESULTS: The opt-in internet opinion panels proved a quick way (19days) to obtain reliable information with a low error margin (3.7%). The online survey collected detailed socio-demographic data. Almost all of the women (98%) had heard about the menopause before. Sixty-one percent perceived the menopause as a temporary phase (17% thought it lasted for one or two years and 44% thought it lasted for three to five years) and only 39% realized the menopause would last for the rest of their life. Twenty-three percent of the women reported any kind of impact of the menopause on their quality of life. However, for the other 77% the menopause had resulted in complaints. No differences according to the women's age, level of education or professional status were found in this respect. Sixty-nine percent of the women had 'ever' used some type of treatment for menopausal symptoms and 53% were currently using a treatment. Forty percent of those with more than three symptoms were currently untreated. Of those who were not on hormone replacement therapy (HRT), 61% would not consider taking it (54% were 'strongly opposed' and 7% simply 'opposed'), while 8% would consider asking their doctor for HRT. Among those women who were opposed to HRT, 25% indicated that they were afraid of the increased risk of breast cancer, 34% cited cardiovascular risks and 26% were worried about weight gain. In this Belgian sample, HRT was used significantly more often by French-speaking women (32%) than by Dutch-speaking women (9%) (OR 4.4, p<0.0001). The alternatives to HRT had a high satisfaction rate among users. Relaxation techniques, regular physical activity, acupuncture and avoiding stress had satisfaction rates similar to that with HRT. It was not possible to compare the alternatives in the same women. Nor was it possible to assess whether more pronounced symptoms required a specific treatment. CONCLUSION: Opt-in internet opinion panels proved a quick and efficient way to gather data on menopausal issues in Belgium. Despite the high levels of awareness and knowledge, there is some confusion concerning the duration of the menopause, and its common perception as a temporary condition is likely to mean that the menopausal burden is substantially underestimated. Many symptomatic women are untreated.

A prospective study of nosocomial-infection-related mortality assessed through mortality reviews in 14 hospitals in Northern France.

AIM: To determine the number of deaths associated with nosocomial infection (NI) occurring in French hospitals, and to evaluate the role of hospital mortality reviews in assessing the preventability of NI-associated death. METHODS: The study considered 13,537 consecutive deaths occurring in 14 French hospitals in 2007 and 2008. An expert commission including attending physicians and nurses determined the likelihood that deaths could be attributed to NI, and the preventability of NI and death. FINDINGS: Medical records of the 2355 eligible patients with a McCabe score of 0 or 1 who died more than 48 h after admission were reviewed. Among them, 33% had at least one NI. Death was attributable to NI in 182 patients, and was considered preventable in 35 cases. Among these, 10 deaths were unexpected. CONCLUSION: Extrapolating these figures nationally, approximately 3500 [95% confidence interval (CI) 2605-4036] deaths attributable to NI occur in France annually. Among these, approximately 1300 NIs (95% CI 357-2196) and 800 deaths (95% CI 51-1481) can be considered preventable. Hospital mortality review commissions can help to improve the quality of health care by identifying circumstances associated with NI contributing to death, and targeting specific preventative measures. Such hospital commissions should involve all healthcare personnel.

The isolated sympathetic spinal cord: Cardiovascular and sudomotor assessment in spinal cord injury patients: A literature survey.

OBJECTIVES: To present a comprehensive approach to the assessment of the severity of the autonomic lesion in spinal cord injury (SCI) patients, with regard to the level of lesion. To discuss how to assess an isolated sympathetic spinal cord that has lost supraspinal control (sympathetically complete lesion). METHOD: PubMed was searched for articles related to cardiovascular (mainly cold pressor test, respiratory and postural challenges) and sudomotor (sympathetic skin responses) tests that have been used. The results of these evaluations are analysed with regard to the site of stimulation (above or below the lesion) according to three types of SCI that offer typical autonomic reactions (tetraplegics, paraplegics at T6 and at T10). RESULTS: Non-invasive cardiovascular and sudomotor testing allows the assessment of the isolated sympathetic spinal cord in SCI patients. Typical responses are found in relation with the level of the sympathetic lesion. Its definition would allow comparison with the somatic motor and sensory level of lesion of SCI patients and provide additional aid to the classification of those patients. CONCLUSION: For research purposes on the integrity of the spinal sympathetic pathways, a battery of test approach is probably needed, using a combination of stimuli above and below the lesion, evaluating both cardiovascular and sudomotor pathways.

Retrovirus-mediated gene transfer into T cells: 95% transduction efficiency without further in vitro selection.

This study was designed to retrovirally transduce T cells by a protocol that would be simple, short, cost effective, applicable for clinical use, and efficient enough to avoid further selection of transduced T cells. Because retrovirally mediated infection is depending on the cell cycle, we first optimized the conditions for activating T cells in the presence of immobilized CD3 monoclonal antibodies and recombinant interleukin 2. Cell cycle analysis indicated that CD8+ and total T cells reach a maximum of cycling within 4 days whereas CD4+ T cells attain their maximum of cycling only by day 6. Taking into account these data, CD4+, CD8+, and total T cells were preactivated for 5 and 3 days, respectively, and then infected for 24 hr with supernatant containing retrovirus pseudotyped with gibbon-ape leukemia virus envelope, using a cell centrifugation protocol. Results show that approximately 95% of CD4+, CD8+, and total T cells can be transduced, this transduction efficiency being significantly higher than that obtained with amphotropic retrovirus vectors. Furthermore, under permanent growth stimulation, transduced T cells can be expanded approximately 1,000-fold in 4 weeks of culture with maintenance of transgene expression. However, Immunoscope analysis revealed alterations of T cell repertoire diversity after 2-3 weeks in culture that was not due to retroviral transduction per se. Overall, these data provide evidence that T cells can be transduced at levels that may alleviate the need for both further selection of transduced cells and in vitro expansion, thereby preserving the repertoire diversity of the transduced T cells to be reinfused.

The outcome of the parasitic process initiated by Leishmania infantum in laboratory mice: a tissue-dependent pattern controlled by the Lsh and MHC loci.

Human visceral leishmaniasis is mainly due to intracellular protozoan parasites of the Leishmania donovani complex, i.e., L. donovani and L. infantum (or L. chagasi). A mouse model has been established to monitor 1) the parasitic process initiated by L. infantum in three tissues they invade, and 2) parameters of the acquired immune response they trigger. Mice congenic at the Lsh locus and mice of inbred strains differing at the MHC locus have been inoculated by the i.v. route with L. infantum. The parasitic process has been evaluated by the follow-up of the parasitic load in the liver, the spleen, and, for the first time, in the bone marrow using a very sensitive limiting dilution assay. As previously established for L. donovani, the early outcome of L. infantum is also under the control of the Lsh locus in the liver; genes of the MHC complex are involved in the development of the subsequent acquired immune response. "Cure" or "noncure" haplotypes are the same for the two species of Leishmania; as far as the cure haplotype is concerned, whatever the tissues being screened, the parasites are never totally cleared, although the liver is the tissue in which the best parasite load reduction is achieved. Through immunostaining, it was established that sialoadhesin-positive stromal bone marrow macrophages contain parasites; such long-lived mononuclear phagocytes could be the host cells where the parasite can find "safe targets" unreactive to the dominant effector immune mechanism triggered by the replicative stage of the parasites.

[Stability control of a copper histidinate solution]. / Contrôle de la stabilité d'une solution d'histidinate de cuivre.

Some authors have suggested the administration subcutaneous of copper histidinate for the treatment of the Menkes disease. The purpose of this study was to control the complex formation of Cu (II)-L-Histidine in molar ratio 1/2 and to verify the stability in some conditions of determination and validation production.

Parasite-host relationships: in-situ study of Leishmania spp. in resistant and susceptible mice.

The host's skin is a critical tissue in the natural life cycle of the Leishmania spp. known to cause an 'asymptomatic' infectious process or cutaneous or visceral leishmaniasis in mammals. The dermis, once disturbed by the inoculation of infective parasites, becomes a site of dynamic events, the progression of which depends upon both host and parasite characteristics. Whatever the final site of the morbidity caused by the parasites, whether it be cutaneous, visceral or muco-cutanous, this site reflects the parasite and host's ability to create a pro- or anti-parasite micro-environment. The characteristics of this environment are now amenable to analysis in situ, as illustrated by the study of the cutaneous processes initiated by inoculation of Leishmania major in laboratory mice.

Transient inducible events in different tissues: in situ studies in the context of the development and expression of the immune responses to intracellular pathogens.

Intracellular pathogens whether facultative like Mycobacterium sp., e.g. Bacillus Calmette Guérin, Listeria monocytogenes or strictly intracellular like Leishmania sp. initiate either asymptomatic infectious processes or disease depending both on factors of the host (genetic as well as environmental ones) and the infectious/pathogenic agents. In this contribution, we first summarized informations which justify to develop in situ analysis to decipher the sequential events that result in different modes/classes of immune responses. How the mode of the immune response is determined remains a main question to address. Although it has recently become clear, in vitro, that immunocompetent cells and their cytokines are critical to set on a stable mode of immune response, acting on naive T cells, this area deserves more in vivo studies. Indeed, peripheral T cells, at different stages of differentiation, may exist in vivo (a) naive/virgin, (b) experienced, (c) effector T cells, depending on the level of stimulation of the immune system by either endogenous or exogenous (e.g. gut flora) signals. The three chosen examples illustrate our contributions in this field focusing on three different non-lymphoid tissues which may become infected: bone marrow (Bacille de Calmette Guérin), liver (Listeria monocytogenes), skin (Leishmania major). These three illustrations also allow to attract attention on the interest of using mice of genetically different strains the immune response of which is set up under different modes.

Training of speech therapists and a psychological profile of the profession.

The psychological professional profile of 20 speech therapists has been investigated by Achtnich's BBT test. The results show three trends common to the profession: choice of the social factor, intense need for imagination and creativity, desire of self-assertion. However, the need for information and acquisition of new knowledge and control of activity is virtually absent among the sample tested.

Influence of rifampicin, phenobarbital and cimetidine on mixed function monooxygenase in extensive and poor metabolizers of debrisoquine.

The effect of enzyme induction by rifampicin and phenobarbital and enzyme inhibition by cimetidine on the hepatic mixed-function monooxygenase (MFO) was investigated in 11 non-smokers, healthy male volunteers. Five were classified as extensive metabolizers (EM) of debrisoquine and 6 as poor metabolizers (PM). Rifampicin (600 mg/day), phenobarbital (100 mg/day) and cimetidine (1.2 g/day) were given for 8, 14 and 4 days, respectively. In PM on rifampicin, the debrisoquine metabolic ratio (MR) was significantly reduced, even reaching a value less than 12.6 in 2 subjects but on phenobarbital and cimetidine, the MR was not significantly modified. In PM on rifampicin and phenobarbital, the urinary excretion of 6 beta-hydroxycortisol was significantly enhanced but not in EM on these drugs. In both groups on cimetidine, salivary antipyrine half-life was lengthened and on rifampicin, it was shortened. In EM and PM on cimetidine, the total oral clearance of antipyrine was lowered but on rifampicin it was solely increased in PM. Regarding the metabolic clearance to the three main urinary antipyrine metabolites, that of norantipyrine (NORA) was significantly increased in PM on rifampicin. In PM on cimetidine, the metabolic clearance of NORA and hydroxymethylantipyrine (HMA) was reduced but in EM that of hydroxyantipyrine was additionally decreased. In PM on rifampicin, the induction of the hepatic mixed-function oxidase system, assessed by the urinary excretion of 6 beta-hydroxycortisol, the salivary antipyrine half-life and total oral clearance and the metabolic clearance of urinary NORA, were shown. On the other hand in PM, cimetidine, a probe drug used for inhibition of the MFO system, made it impossible to distinguish PM from EM.

Simvastatin (MK 733) in heterozygous familial hypercholesterolemia: a two-year trial.

Simvastatin (MK 733), a new competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, given in daily doses of 20 mg and 40 mg for 104 weeks, has been shown to lower the serum total cholesterol and low density lipoprotein cholesterol level by more than 30% and the serum apoprotein B level by 20% in 19 adult patients with heterozygous familial hypercholesterolemia. A slight but non-significant increase of high density lipoprotein cholesterol levels was shown throughout the trial with significant elevation of the serum apoproteins AI and AII only observed at week 52. Mild and transient clinical or biochemical (increases of creatine phosphokinase and transaminases) side effects, observed in some patients, did not necessitate the withdrawal of the medication. Full ophthalmological examinations did not reveal ocular disturbances, particularly no apparent increase of lens opacities, during the trial. Simvastatin seems to be an effective and safe drug as monotherapy in the treatment of heterozygous familial hypercholesterolemia.

Plasma glucose, insulin, glucagon and prolactin during long lasting lactation.

Circulating levels of glucose and particularly those of insulin are significantly lower in African mothers (Kivu, Zaire) nursing their infants than in non pregnant and non lactating women of the same area. Furthermore, the glycemia and the insulinemia increase relatively less after a glucose load in the breastfeeding mothers. The lack of glucose available to the mammary gland may explain the low volumes of milk produced by the lactating mothers in this region of Africa.