Potential market size and impact of hepatitis C treatment in low- and middle-income countries.

The introduction of direct-acting antiviral agents (DAAs) has made hepatitis C infection curable in the vast majority of cases and the elimination of the infection possible. Although initially too costly for large-scale use, recent reductions in DAA prices in some low- and middle-income countries (LaMICs) has improved the prospect of many people having access to these drugs/medications in the future. This article assesses the pricing and financing conditions under which the uptake of DAAs can increase to the point where the elimination of the disease in LaMICs is feasible. A Markov simulation model is used to study the dynamics of the infection with the introduction of treatment over a 10-year period. The impact on HCV-related mortality and HCV incidence is assessed under different financing scenarios assuming that the cost of the drugs is completely paid for out-of-pocket or reduced through either subsidy or drug price decreases. It is also assessed under different diagnostic and service delivery capacity scenarios separately for low-income (LIC), lower-middle-income (LMIC) and upper-middle-income countries (UMIC). Monte Carlo simulations are used for sensitivity analyses. At a price of US$ 1680 per 12-week treatment duration (based on negotiated Egyptian prices for an all oral two-DAA regimen), most of the people infected in LICs and LMICs would have limited access to treatment without subsidy or significant drug price decreases. However, people in UMICs would be able to access it even in the absence of a subsidy. For HCV treatment to have a significant impact on mortality and incidence, a significant scaling-up of diagnostic and service delivery capacity for HCV infection is needed.

Developmental determinants in non-communicable chronic diseases and ageing.

Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.

Blood libel rebooted: traditional scapegoats, online media, and the H1N1 epidemic.

This study of comments posted on major French print and TV media websites during the H1N1 epidemic illustrates the relationship between the traditional media and social media in responding to an emerging disease. A disturbing "geography of blame" was observed suggesting the metamorphosis of the folk-devil phenomenon to the Internet. We discovered a subterranean discourse about the putative origins and "objectives" of the H1N1 virus, which was absent from the discussions in mainstream television channels and large-circulation print media. These online rumours attributed hidden motives to governments, pharmaceutical companies, and figures of Otherness that were scapegoated in the social history of previous European epidemics, notably Freemasons and Jews.

Does cancer survivors' health-related quality of life depend on cancer type? Findings from a large French national sample 2 years after cancer diagnosis.

We investigated whether health-related quality of life (HRQL) depends on cancer type, after adjustment for demographic and medical variables. A French national population-based survey was conducted between November and December 2004 to assess surviving cancer patients' HRQL 2 years after diagnosis. HRQL was measured by the 36-Item Short Form Survey scale. The sample included 3900 persons. All cancer diagnoses were entered in the study. We demonstrated that medical and treatment variables have an impact on patients' physical HRQL but not on mental HRQL. Cancer type impacted on physical HRQL, with those suffering from upper aerodigestive tract /lung cancers and haematological malignancies being affected to a greater degree. Disturbing side effects impacted both HRQL domains. Socio-demographic variables had statistically significant effects but not clinically meaningful ones. Socio-economic variables led to potentially clinically meaningful differences for cancer patients' HRQL and represented a socio-economic gradient in HRQL among cancer survivors. From our results, we may assert that cancer survivors, 2 years after cancer diagnosis, share a similar pattern of psychological morbidity, independent of cancer type. Patients disproportionately affected by cancer, such as those with lower educational levels and income, need to be identified and targeted and interventions which address their unique needs and concerns need to be developed.

[Study of the intra- and extracellular electrolyte content in Paramecia cultures carried out during a space flight (author's transl)]. / Etude de la teneur intra et extracellulaire des electrolytes dans les cultures de Paramecies réalisées pendant un vol spatial.

In the results of previous investigations we have already reported that cultures of Paramecium tetraurelia submitted to a space flight present a stimulation of their proliferative ability, an increase in cell volume and a decrease in dry weight and in total protein content. These results suggest changes of cell metabolism induced by the space environment. In order to confirm this hypothesis we have studied the concentration of extracellular electrolytes in the control and the in-flight culture media with respect to the intracellular content of the same electrolytes. These measures concern Na, Cl, K, P, Mg, Ca. In this paper we report the results of these analyses and note that if no differences are noted for Na and Cl between control and in-flight cultures, modifications in P, K, Ca and Mg levels are observed. Generally there is a higher concentration of these elements in the in-flight medium but, in contrast, a lower intracellular content is noted for in-flight Paramecia. We have established a double comparison: on the one hand between control and in-flight media and between control and in flight cells, on the other hand between media and cells. All these data suggest possible changes in the membrane permeability, or of the binding proteins in Paramecia cultivated in hypogravity.

Evidence for the activation of phospholipases during acrosome reaction of human sperm elicited by calcium ionophore A23187.

Incubation of washed human sperm with [3H]- or [14C]arachidonic acid allowed a major incorporation of the label into phospholipids, provided that the final concentration of the fatty acid did not exceed 20 microM. A further challenge with calcium ionophore A23187 of spermatozoa suspended in a calcium-containing medium led to phospholipid hydrolysis, which could account for 10-12% of total cell radioactivity. Degradation products were identified as free, unconverted arachidonic acid, occurring with some diacylglycerol. Phospholipid hydrolysis was significant after 15 min of incubation and became maximal after 120 min. It was found to be calcium dependent, diacylglycerol and free arachidonate production occurring maximally at 2 mM and 5 mM CaCl2, respectively. Phosphatidylcholine and phosphatidylinositol were the most significantly degraded phospholipids after 60 min of incubation. Similar incubations conducted with 32P-labeled sperm confirmed the selective hydrolysis of phosphatidylcholine and revealed an increase production of phosphatidic acid probably due to a phosphorylation of diacylglycerol. Under the same conditions, one third of the cells remained motile and electron microscopy revealed that acrosome reaction was completed in 40% of the cells and displayed an intermediary state in 40-50% of the spermatozoa. Furthermore, a good parallelism was observed between the extent of the acrosome reaction and the extent of phospholipid hydrolysis promoted by increasing concentrations of A23187. It is concluded that calcium entry into the cells activates both a phospholipase A2 and a phospholipase C, leading to the production of substances, like lysophospholipid, diacylglycerol or phosphatidic acid, which may or may not be involved in acrosome reaction.

High-dose sequential chemotherapy with recombinant granulocyte colony-stimulating factor and repeated stem-cell support for inflammatory breast cancer patients: does impact on quality of life jeopardize feasibility and acceptability of treatment?

PURPOSE: This study was designed to investigate the quality of life (QOL) of patients enrolled onto the High-Dose Chemotherapy for Breast Cancer Study Group trial (PEGASE 02), a French pilot multicenter trial of the treatment of inflammatory breast cancer (IBC) aimed at evaluating (1) toxicity and feasibility of sequential high-dose chemotherapy (HDC) with recombinant human granulocyte colony-stimulating factor (filgrastim) and stem-cell support and (2) response to HDC in terms of pathologic response and survival. PATIENTS AND METHODS: QOL measures were performed at inclusion and four times subsequently up to 1 year using an ad hoc side-effect questionnaire (19 physical symptoms) and the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30). RESULTS: Of the 95 patients entered, the overall QOL questionnaire completion compliance was 75.6%. During cycle 3 of HDC, the number of symptoms was high (mean +/- SD QOL score, 10 +/- 3), with fatigue, hair loss, appetite loss, nausea, change in taste, vomiting, fever, and weight loss reported by more than 60% of patients. Toxicity and distress associated with HDC were reflected in the decline of four EORTC QLQ-C30 scores: global QOL (P =.001), and physical, role, and social functioning (P <.001 for all statistics). However, QOL deterioration disappeared after treatment completion, except for physical functioning (P =.025). One year after inclusion, most QOL scores returned to baseline, and both emotional functioning and global QOL scores were even higher than baseline (P =.030 and P =.009, respectively). CONCLUSION: If it is confirmed that improvements in pathologic response rates with HDC effectively translate into increased probabilities of survival for IBC patients, adoption of such treatment as PEGASE 02 will not involve crucial choices between length of life and QOL and should not be delayed for QOL arguments.

Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Société Française de Greffe de Moelle.

PURPOSE: To compare hematologic recovery in patients receiving allogeneic blood cell transplantation (BCT) with those receiving allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: One hundred eleven patients with leukemia in the early stages and with HLA-matched sibling donors were randomized in this study. One hundred one underwent transplantation. Standard procedures for collection and transplantation were used. Patients did not receive prophylactic granulocyte colony-stimulating factor after undergoing transplantation. In addition to clinical end points being established, a prospective and comparative economic evaluation of the first 6 months after transplantation was performed. RESULTS: Groups were balanced for patient, donor, and transplant characteristics. Blood cell collection led to the collection of a higher number of CD34(+) and CD3(+) cells than did bone marrow collection (P < 10(-6)) without reported side effects for the donor. Patients in the BCT group reached platelet counts of 25 and 50 x 10(9) platelets/L 8 and 11 days earlier than did the BMT group (P < 10(-4) and P < 10(-5)), respectively. This resulted in fewer platelet transfusions during the first 180 days after transplantation (P =.002) for the former group. The time to reach neutrophil counts of 0.5 and 1 x 10(9) neutrophils/L was 6 and 7 days shorter, respectively, in the BCT group than in the BMT group (P < 10(-5)). This quicker hematologic recovery was associated with a shorter length of hospitalization and a decrease in total cost of procedure during the first 6 months. CONCLUSION: This study establishes that allogeneic BCT results in quicker hematologic recovery but is associated with a higher occurrence of chronic graft-versus-host disease.

Attitudes toward palliative care, conceptions of euthanasia and opinions about its legalization among French physicians.

We assume that actors of the professionalization process of palliative care make a special effort to demarcate it from euthanasia, and that such an effort has a significant impact on beliefs and attitudes toward euthanasia among the whole medical profession. We investigated concurrently attitudes toward palliative care, conceptions of euthanasia and opinion toward its legalization among a sample of 883 French general practitioners, oncologists and neurologists. We found four contrasted profiles of attitudes toward palliative care, which were closely correlated with being in touch with palliative care providers. Attitudes toward palliative care were closely correlated with beliefs about which medical practices should be labelled euthanasia, and these beliefs were in turn strongly associated with opinions toward euthanasia legalization. Our results suggest that the relationship between palliative care and euthanasia mixes semantic and strategic aspects, beyond cognitive and conative ones.

Disclosure of prognosis to terminally ill patients: attitudes and practices among French physicians.

BACKGROUND: Disclosure of the prognosis to terminally ill patients is a strong prerequisite for integrating the physical, psychological, spiritual, and social aspects of end-of-life care. OBJECTIVE: This study aimed to assess French physicians' general attitudes and effective practices (with patients followed up to death recently) toward such disclosure. DESIGN/SUBJECTS: We used data from a cross-sectional survey conducted among a national sample of 917 French general practitioners, oncologists, and neurologists. RESULTS: A majority of respondents opted for prognosis disclosure only at patients' request, very few opted for systematic disclosure without patient's request, and a significant minority opted for systematic concealment. Concerning deceased patients described by respondents, 44.5% of competent patients were informed of prognosis by their physician, 27.3% were informed by someone else, 9.0% refused to be informed, and 19.2% were simply not informed. Concealment was more frequent for older patients, and physicians involved in a nongovernmental organization (NGO) for patients' support were more likely to disclose the prognosis, even without patient's request. CONCLUSIONS: Disclosure of the prognosis to terminally ill patients is still far from systematic in France. Further research is needed to better understand the motivations of French physicians' disclosure practices, which are probably culturally shaped.

Misconceptions about transmission of AIDS and attitudes toward prevention in the French general public.

A survey of the social perception of AIDS and its prevention was carried out in December 1987 in a representative sample of the adult population of the Paris region (France). A significant part of the general public still holds misconceptions about transmission by casual contact and blood donation. Misbeliefs about modes of transmission clearly encourage individuals' willingness to stigmatize AIDS patients and to support the most coercive measures of prevention (such as quarantine). Advertizing efforts to promote use of condoms, sexual education in schools, and systematic HIV screening for pregnant women are the only measures which create a broad consensus independently of sociocultural differences. Socioeconomic status and even religious or political beliefs strongly influence public opinions toward other preventive measures.

Adherence to HAART in French HIV-infected injecting drug users: the contribution of buprenorphine drug maintenance treatment. The Manif 2000 study group.

OBJECTIVES: To assess adherence to highly active antiretroviral therapies (HAART) in a cohort of French patients infected by HIV through injection drug use (IDU), and the impact on adherence of buprenorphine ambulatory drug maintenance treatment (DMT) which has been widely introduced since 1996. DESIGN: Adherence assessment at first visit after initiation of HAART in the MANIF2000 cohort study. METHODS: Patient's face-to-face and self-administered questionnaires. Univariate and logistic regression adjusted odds ratios (OR) to compare characteristics of non-adherent versus adherent patients. RESULTS: Of the 164 patients, 34.8% took less than 80% of the prescribed HAART doses during the previous week. Decrease in viral load titres after initiation of HAART was significantly lower among non-adherent patients. After adjustment by logistic regression, non-adherence was associated with younger age, alcohol consumption, frequency of negative life-events during the prior 6 months and active drug use. However, IDU in buprenorphine DMT reached higher levels of adherence (78.1%) than ex-IDU (65.5%), although this difference did not reach statistical significance. CONCLUSION: Prescription of buprenorphine DMT may increase adherence to HAART among HIV-infected opiate-dependent patients. Reducing the negative impact of stressful life-events through psychosocial interventions should be considered, even for those who have stopped using drugs.

HIV testing, HIV infection and associated risk factors among inmates in south-eastern French prisons.

OBJECTIVES: To estimate HIV seroprevalence in the two main remand and short-stay prisons of south-eastern France and to gather linked anonymous risk-factor information. SETTING: Baumettes prison, Marseille, France between 16 November and 21 December 1992. PARTICIPANTS: Using a self-administered questionnaire about HIV testing and risk factors for HIV infection, 295 male and 137 female inmates were interviewed. The response rate was 96% (100 and 90% for men and women, respectively). At the same time, 279 of a total of 432 (65%) inmates were serologically tested for HIV; 153 (35%) declined to provide a blood sample. DESIGN: Anonymous cross-sectional and surveillance survey. RESULTS: Twenty per cent of participants (84 our of 432) were intravenous drug (heroin) users (IVDU), 51% of whom reported needle-sharing prior to incarceration; 23% reported more than two sexual partners during the last year, and 13% sexual intercourse with an IVDU during the last 5 years. HIV status was available for 356 inmates (82%; 65% from blood samples and 17% from the questionnaire); 39 were HIV-infected (10.9%; 95% confidence interval, 7.7-14.2). The inmates not tested for HIV reported proportionally less risky behaviours than non-HIV-infected inmates. HIV seroprevalence was significantly higher among recidivist inmates (19.9 versus 4.4%; P < 0.0001). The rate of HIV infection was particularly high among IVDU (34 out of 84; 40%). More female non-IVDU were HIV-infected than male non-IVDU (4.1 versus 0.6%; P = 0.04). CONCLUSIONS: This study demonstrates the high prevalence of HIV infection in south-eastern French prisons, especially among IVDU. The rates may be related to the high prevalence of risky drug practices and to delays in the development of HIV prevention programmes for IVDU in France. The higher seroprevalence rate among recidivist inmates might be the result of risk behaviours during imprisonment. Another hypothesis is that recidivist inmates are at greater risk of HIV infection because of higher levels of drug use.

Failure to maintain long-term adherence to highly active antiretroviral therapy: the role of lipodystrophy.

In a sample of 277 patients included in the French APROCO cohort study who were initially adherent at follow-up visit 4 months after initiation of a protease inhibitor-containing regimen, 76.4% self-reported at least one lipodystrophy-related symptom and 30.0% failed to maintain adherence behaviour 20 months after enrolment. After multiple adjustment for other related factors, such as younger age, alcohol consumption and poor housing conditions, the number of self-reported lipodystrophy symptoms was independently associated with adherence failure.

Physicians' attitudes towards mammography and prophylactic surgery for hereditary breast/ovarian cancer risk and subsequently published guidelines.

After a BRCA mutation has been identified in the context of hereditary breast/ovarian cancer (HBOC), mammographic screening and prophylactic surgery are two of the main options available to those responsible for the clinical management of healthy women. The aim of this study was to describe the attitudes of specialists towards the clinical management of women with an HBOC risk: this information was collected prior to the publication of the recent French guidelines. A random national sample of 1169 French surgeons, gynaecologists and obstetricians was surveyed using a mailed questionnaire, to which 700 of these physicians (60%) responded. When dealing with a BRCA mutated woman, 88.6% of the respondents said they would recommend mammographic screening, but only 27.1% would recommend that it should be carried out annually from the age of 30 years onwards, as recommended in the French guidelines; 10.9% would find it acceptable to propose prophylactic mastectomy from the age of 30 years, and 22.9% would find it acceptable to propose prophylactic oophorectomy from the age of 35 years. The specialists who agreed with recommending breast/ovarian cancer genetic testing also had more positive attitudes towards prophylactic mastectomy (adj OR = 3.4, 95% CI = 1.4-8.2), as did those who had previously recommended prophylactic mastectomy when gene testing was not yet available (adj OR = 2.06, 95% CI = 1.23-3.44). The respondents' attitudes towards prophylactic oophorectomy and mastectomy were significantly associated (adj OR = 3.9; 95% CI = 2.3-6.5). Previous recommendation of prophylactic mastectomy was associated (P < 0.01) with a higher level of knowledge of breast/ovarian cancer genetics and with medical practice in this field. French physicians' attitudes towards mammographic screening and prophylactic surgery were not in complete agreement with the subsequently published French guidelines, the impact of which has now to be considered. Constantly evolving knowledge about the efficacy of preventive intervention will give practitioners new elements to integrate into their counselling.

Compared effects of a low and a high sodium diet on the renal and urinary concentration and activity of kallikrein in normal rats.

Different sodium intakes may affect or alter the urinary excretion of renal kallikrein. We have compared the renal and the urinary effects of sodium depletion and sodium loading with 1% NaCl on total kallikrein, using a direct radio-immunoassay against immunoreactive kallikrein and on active kallikrein assessed by a kininogenase assay with a kinin radio-immunoassay. Sodium depletion resulted in an increase in renal and urinary excretion of both the immunoreactive kallikrein and the kininogenase activity. Sodium loading resulted in a slight but significant decrease in renal tissue immunoreactive kallikrein content without any change in the kininogenase activity, while the urinary excretion of the kininogenase activity was greatly increased and the urinary immunoreactive kallikrein remained steady. This sodium depletion induces consistent effects at the renal and urinary level, resulting probably from a stimulation of biosynthesis. However, during sodium loading, renal and urinary measurements of kallikrein are dissociated. Furthermore, kininogenase activity and immunoreactive kallikrein are not correlated in either of the two studied compartments. Thus sodium loading seems to induce independent effects at the renal and urinary levels, possibly resulting from different mechanisms.

Effects of pinacidil on the sympatho-adrenal system in dogs.

1. The aim of the present work was to study the antihypertensive effect of pinacidil, a potassium channel opener, in sinoaortic denervated (SAD) conscious dogs and to investigate whether the involvement of the sympathetic nervous system induced by this vasodilator compound is only of baroceptor reflex origin. 2. Pinacidil (0.1, 0.2, 0.4 mg kg-1 i.v.) induced a dose-dependent decrease in blood pressure in normal as well as in SAD dogs. In contrast, the induced-tachycardia observed in normal dogs was not found in SAD animals. 3. Since pinacidil induced an increase in plasma catecholamines, free fatty acids, glucose, plasma renin activity and aldosterone in SAD dogs it is suggested that this sympathetic activation is independent of the baroreceptor reflex pathways. 4. The sympathetic activation is mainly of peripheral origin, since pinacidil (0.7 mg kg-1 i.v.) induced an increase in adrenaline release from the adrenal gland after section of the great splanchnic nerve in anaesthetized dogs. This increase is probably due to an effect that does not involve K+ channel opening. However, this effect of pinacidil was not observed during splanchnic nerve stimulation (in this case, the involvement of K+ channel opening is suggested).