Evaluation of patient reported outcome measures and costs of managing osteoarthritis of the hip.

The number of hospital admissions for a hip prosthesis increased by more than 91% between 2002 and 2019 in Belgium (1), making it one of the most common interventions in hospitals. The objective of this study is to evaluate patient-report- ed outcomes and hospital costs of hip replacement six months after surgery. Both generic (EQ-5D) and specific (HOOS) PROMs of general hospital patients undergoing hip replacement surgery in 2021 were conducted. The results of these PROMs were then combined with financial and health management data. The mean difference (SD) in QALYs between the preoperative and postoperative phases is 0.20 QALYs (0.32 QALYs). The average cost (SD) of all stays is €4,792 (€1,640). Amongst the five dimensions evaluated in the EQ-5D health questionnaire, the 'pain' dimension seems to be associated with the greatest improvement in quality of life. As regards Belgium, the 26,066 arthroplasties performed in 2020 might constitute a gain of 123,000 years of life in good health. The relationship between QALYs and costs described in this study posits a ratio of €23,960 per year of life gained in good health. Given that in Belgium more than 3% of the hospital healthcare budget is devoted to hip prostheses, it would seem relevant to us to apply PROM tools to the entire patient population to assess treatment effectiveness more broadly, identify patient needs and, also, monitor the quality of care provided.

[Study of cancer risks associated with Lynch syndrome in the Liège region]. / Etude des risques oncologiques associés au syndrome de Lynch en région liégeoise.

Lynch syndrome is a hereditary predisposition to several cancers. The goals of our study were to know the different mutations in our Lynch population, to evaluate the prevalence of cancers in this population and to determine the mean age of onset of those cancers. This retrospective study includes proven carriers of a MMR mutation diagnosed either by the CHU of Liège or either by the CHC Saint-Joseph in Liège, Belgium. We noted a clear majority of MSH2 mutations (50 %) in the Lynch families recorded in Liège, which is different from the main literature. In our study population (106 subjects), 65 % of subjects were affected by at least one cancer. Prevalences for colorectal and endometrial cancers are, respectively, 50 % and 27.5 %. We found no difference in the mean age of onset of cancers compared to literature. We discuss the follow-up of Lynch patients and the interest of additional exams such as hysteroscopy and cystoscopy.

Le syndrome de Lynch est un syndrome de prédisposition héréditaire à un certain nombre de cancers. Les objectifs de notre étude sont de connaître la répartition des différentes mutations dans la population Lynch prise en charge dans nos centres, d'évaluer la prévalence des cancers présentés par les patients Lynch de cette population et de déterminer l'âge moyen d'apparition de ces cancers. Cette étude rétrospective inclut les porteurs confirmés d'une mutation MMR ayant été diagnostiqués, soit par le CHU de Liège, soit par le CHC Saint-Joseph à Liège. Nous avons constaté une nette majorité de mutations MSH2 (50 %) parmi les familles Lynch répertoriées à Liège, ce qui est différent de ce qui est décrit dans la littérature. Dans notre population d'étude (106 sujets), 65 % des sujets ont présenté au moins un cancer. Les prévalences du cancer colorectal et de l'endomètre sont, respectivement, de 50 % et 27.5 %. Nous n'avons pas trouvé de différence dans les âges moyens de présentation des cancers par rapport à la littérature existante. Nous discutons du suivi des patients porteurs d'un syndrome de Lynch et de la place d'examens supplémentaires comme l'hystéroscopie et la cystoscopie.

[Chronic autoimmune gastritis : a multidisciplinary management]. / La gastrite chronique auto-immune : une prise en charge multidisciplinaire.

Chronic autoimmune gastritis (CAG) is a continuum of histological changes in gastric mucosa including: atrophy, intestinal metaplasia, dysplasia and finally, the occurrence of a neoplasm (gastric Neuroendocrine Tumors -NETs- and adenocarcinoma). The association with Hashimoto and Graves-Basedow disease is known as the thyrogastric autoimmune syndrome. While Helicobacter pylori (Hp) infection may be associated with CAG, the role of the gastric microbiota is ill-defined. The gastric hypochlorhydria determines a malabsorption of different micronutrients (iron, magnesium, calcium, vitamin B12) as well as drugs (thyroxine, etc.). Pernicious anemia is favoured by the deficit of parietal intrinsic factor that contributes to B12 malabsorption. Serology for Hp, serum pepsinogen I/II, increased gastrin levels, the presence of parietal cell antibodies and intrinsic factor antibodies may reveal CAG. High definition endoscopy associated with virtual chromoendoscopy seems promising for CAG diagnosis and follow-up. NETs type 1 treatment includes: endoscopic and surgical resection, somatostatin analogues and the recent availability of netazepide, a gastrin antagonist. We review herein advances in the treatment and diagnosis of CAG and associated autoimmune disorders, which may involve, in a multidisciplinary way, all practitioners.

La gastrite chronique auto-immune (GAI) est un continuum d'altérations de la muqueuse gastrique incluant : atrophie, métaplasie intestinale, dysplasie et, enfin, la survenue d'une néoplasie (tumeurs neuroendocrines [NETs] gastriques et adénocarcinome). L'association avec la maladie de Hashimoto et de Graves-Basedow est connue comme syndrome thyrogastrique auto-immun. Alors que l'Helicobacter pylori (Hp) peut s'associer avec la GAI, le rôle du microbiote gastrique est mal défini. L'hypochlorhydrie gastrique détermine une malabsorption de micronutriments (fer, magnésium, calcium, vitamine B12) et de médicaments (thyroxine et autres). L'anémie de Biermer est favorisée par le déficit de production du facteur intrinsèque pariétal, contribuant à la malabsorption de B12. Un rapport diminué de pepsinogène I/II, une augmentation de la gastrine, la présence d'anticorps anti-cellule pariétale, les anticorps anti-facteur intrinsèque et la sérologie pour Hp contribuent à révéler précocement le diagnostic de GAI. L'endoscopie haute définition, associée à la chromoendoscopie virtuelle, semble prometteuse dans le diagnostic et dans le suivi. Le traitement des NETs gastriques de type 1, favorisées par la GAI, inclut : la résection endoscopique/chirurgicale, les analogues de la somatostatine et l'antagoniste de la gastrine nétazépide. Nous résumons ici les avancées diagnostiques et thérapeutiques dans la GAI et dans les affections associées : elles impliquent, de façon multidisciplinaire, l'ensemble des praticiens.

[Cost evaluation of organ harvesting in a Belgian academic hospital]. / Evaluation du coût de revient des prélèvements d'organes effectués dans le cadre de l'activité de transplantation d'un centre universitaire belge.

INTRODUCTION: The aim of this study is (1) to describe the characteristics of the organ harvesting activity conducted in 2012 at the Erasme's Hospital, Brussels University Hospital, (2) to highlight the different combinations " type of donor/types of organ's retrieved " in relation to organ harvestings carried out within the hospital, and (3) to calculate the organ harvesting's cost of acts. METHODS: The study is conducted according to the hospital perspective. It assesses the consumption of medical and nursing staff resources, disposable material costs, medical device costs, drugs costs, sterile instruments and biomedical equipment costs, of the 34 organ harvesting procedures that has been conducted this year. Costs are calculated by procedure, by donor's type, by organ and by combinations. RESULTS: Total cost is 99.442 €, with an average cost per donor of 3.016 €, 3.292 € for DBD postmortem donor (Donor Brain Death) and 2.456 € for DCD type (Donor Cardio-Circulatory Death). The average cost per organ leading to a transplantation is 1.842 € for DCD type and 1.297 € for DBD. CONCLUSION: The results show that there is as many costs as the number of organ harvesting's combinations. Integrate the revenue generated by organ harvestings could establish whether funding sources cover the costs generated by this activity or if a reform of the nomenclature should be considered.

INTRODUCTION: Les objectifs de ce travail sont (1) de décrire les caractéristiques de l'activité de prélèvement d'organes réalisée en 2012 par l'Hôpital Erasme, Cliniques Universitaires de Bruxelles, (2) de mettre en évidence les différentes combinaisons " type de donneur/types d'organes prélevés " rencontrées dans le cadre des prélèvements d'organes effectués au sein de l'institution, et (3) de calculer le coût de revient des actes de prélèvement d'organes. Matériel et méthodes : L'évaluation du coût est menée du point de vue du fournisseur de soins. Elle évalue la consommation des ressources en personnel médical et soignant, produits médicaux courants, dispositifs médicaux de viscérosynthèse, spécialités pharmaceutiques, instruments stériles et équipements biomédicaux, de 34 procédures de prélèvement d'organes. Les coûts sont calculés par type de donneur, par organe et par combinaison de prélèvement. Résultats : Le coût total calculé s'élève à 99.442 €, avec un coût moyen par donneur vivant à 3.016 €, par donneur post-mortem de type DBD (Donor Brain Death) à 3.292 €, et de type DCD (Donor Cardio-Circulatory Death) à 2.456 €. Par organe prélevé ayant abouti à la transplantation, le coût moyen est de 1.842 € lorsqu'il provient d'un donneur de type DCD, et de 1.297 € s'il provient d'un donneur de type DBD. CONCLUSION: Les résultats montrent qu'il y a autant de coûts de prélèvement que de combinaisons de prélèvement. Intégrer les recettes générées par les prélèvements permettrait d'établir si les sources de financement couvrent les frais engendrés par cette activité, ou si une réforme de la nomenclature devrait être envisagée dans ce secteur d'activité.

The neuroinflammatory response in humans after traumatic brain injury.

AIMS: Traumatic brain injury is a significant cause of morbidity and mortality worldwide. An epidemiological association between head injury and long-term cognitive decline has been described for many years and recent clinical studies have highlighted functional impairment within 12 months of a mild head injury. In addition chronic traumatic encephalopathy is a recently described condition in cases of repetitive head injury. There are shared mechanisms between traumatic brain injury and Alzheimer's disease, and it has been hypothesized that neuroinflammation, in the form of microglial activation, may be a mechanism underlying chronic neurodegenerative processes after traumatic brain injury. METHODS: This study assessed the microglial reaction after head injury in a range of ages and survival periods, from <24-h survival through to 47-year survival. Immunohistochemistry for reactive microglia (CD68 and CR3/43) was performed on human autopsy brain tissue and assessed 'blind' by quantitative image analysis. Head injury cases were compared with age matched controls, and within the traumatic brain injury group cases with diffuse traumatic axonal injury were compared with cases without diffuse traumatic axonal injury. RESULTS: A major finding was a neuroinflammatory response that develops within the first week and persists for several months after traumatic brain injury, but has returned to control levels after several years. In cases with diffuse traumatic axonal injury the microglial reaction is particularly pronounced in the white matter. CONCLUSIONS: These results demonstrate that prolonged microglial activation is a feature of traumatic brain injury, but that the neuroinflammatory response returns to control levels after several years.

Umbilical spider's web.

Question: We report the case of a 38y old woman who consulted for chronic diffuse abdominal pain related to previous irritable bowel syndrome diagnosis. Physical examination showed nonblanching reddish hyperpigmented reticular peri-umbilical skin patch (figure 1). What's your diagnosis? Answer: The diagnosis of erythema ab igne was made. Additional investigations confirmed repeated use of hot water bottles applied on abdominal wall for 3 weeks overnight for pain relief. Erythema ab igne is a pathognomonic cutaneous presentation of long-lasting exposure to heat sources (1). The pathophysiology of erythema ab igne remains uncertain. It has been suggested that heat exposure damages dermal vascular plexus and subsequent hemosiderin deposition leading to spider's web-like hyperpigmentation. Differential diagnosis of peri -umbilical dermatological manifestations includes digestive-related entities as caput medusae's sign (related to portal hypertension), Cullen's sign or Walzel's sign (related to acute pancreatitis); and non-digestive-related entities such as livedo reticularis (2). Erythema ab igne is well known from the dermatologists, mostly located on the lower limbs due to prolonged close exposition to heaters or on thighs due to laptop batteries (3). Erythema ab igne is usually of benign course, most often self-resolving after heat exposure discontinuation (3). We believe that it is of paramount to take into consideration the patients' pain and to propose an adapted management to avoid self-treatment.

[Are extra costs generated by patients justifiable? Methodology and results from a study carried out in a Belgian general hospital]. / Les surcoûts engendrés par certains patients sont-ils justifiables? Méthodologie et résultats d'une étude réalisée dans un hôpital général belge.

Cost outliers account for 6 to 8% of hospital inpatient stays and concentrate 22 to 30% of inpatient costs. Explanatory factors were highlighted in various studies. They are the lenght of stay, an intensive care unit stay, the severity of illness index related to DRG and social factors. Patients are not always explained by these factors. The objective of this study is to analyse cases not explained by those factors, through a detailed analysis of medical files. In the studied hospital, there are 6,3% high cost outliers and 1,1% low cost outliers. These stays were isolated on the basis of a rule based on percentiles. Extra costs generated by high cost outliers are 6.999 euro per stay. The extra lenght of stay for these patients is 20,42 days. Among the 454 patients high cost outliers, 334 patients are explained by factors extracted from a statistical analysis based on a logistic regression (intensive care unit stay, severity of illness index, lenght of stay and social factors). The analysis of medical files of the 120 not explained inpatient stays highlights new explanatory factors (coding errors, heterogeneity of DRGs, etc.). At the end of this study, the conclusion is that a statistical analysis combined with a precise analysis of medical files allowed to explain the majority of cost outliers. An explanation is however not necessarily synonymous with medical justification.

Immune profile at HIV infection diagnosis: Evolution in the French Alps area over the last 20 years.

OBJECTIVES: Health of HIV-infected people relies on early antiretroviral therapy, i.e. early diagnosis. We aimed to determine whether the characteristics at HIV diagnosis in two French medical centres changed over the last 20 years. PATIENTS AND METHODS: All individuals diagnosed with HIV infection in Grenoble University Hospital (N=814) and Annecy Hospital (N=246) between 1997 and 2015 were included. We collected age, country of birth, mode of transmission, CD4T cell count, CD4/CD8 ratio, and HIV viral load. RESULTS: Among the 1060 patients (mean age 37.4±11 years, 70.2% of men), 42.5% were men having sex with men (MSM); 65.2% were born in France, and 24.4% were born in Africa. Mean CD4T cell count at diagnosis was 396±288/mm3 and was stable over the study period when considering all patients; when considering the MSM group, a significant increase over time was observed, with a mean increase of 7.3 CD4/mm3 per year (P<0.001). A higher CD4 count at diagnosis was observed after 2005 (400±289 vs 468±271/mm3, P=0.005). The proportion of MSM patients with a CD4 count<200/mm3 at diagnosis was lower after 2005 (14.7% after 2005 and 25.6% before, P=0.028) This was not observed in heterosexual patients (born in Africa or not). CONCLUSION: In the MSM population, CD4 count at diagnosis is higher after 2005, suggesting that screening campaigns have become more efficient. This was not observed in other populations, who should be better targeted in future strategies.

Financial consequences of hospital-acquired bacteraemia in three Belgian hospitals in 2003 and 2004.

The financial and human costs of hospital-acquired infections are increasingly recognised in many healthcare systems. This study seeks to quantify excess expenditures on hospital-acquired bacteraemia (HAB) in three Belgian general hospitals in 2003 and 2004. Patients with HAB were compared with patients in the same All Patient Refined Diagnosis Related Groups (APR-DRGs) without HAB. Patient level costs were estimated using a hospital costing system developed by the 'Université Libre de Bruxelles', and compared with DRG-based funding for the three hospitals. HAB incidence was consistent with the national rate for two of the three hospitals, but considerably higher for the third. Both severity of illness and mortality were higher in the HAB group. Nosocomial bacteraemia was associated with an increased length of stay of 30 days and of 6.1 days in intensive care units. When compared with uninfected patients in the same DRG, treatment of HAB patients cost an additional euro 16,709. At current funding rates, hospitals made a mean profit of euro 446 for uninfected patients, but a mean loss of euro 2,431 for patients with HAB. Our findings suggest that hospitals have a financial interest in reducing the rate of HAB, even in a system which funds such complications through severity adjustments in the APR-DRG system. Growing international interest in pay for performance and other funding schemes will only strengthen these financial incentives.

Evaluation of cost and length of stay, linked to complications associated with major surgical procedures.

INTRODUCTION: A lot of studies have demonstrated the possibility of reducing the number of post-operative complications in the domain of major surgical procedures with the use of medical preventive techniques. However, complications following surgical procedures are unfortunately frequent and are a major problem, not only because of the impact for the patient, but also because of economic consequences that they provoke. The aim of the present study is to evaluate the extra length of stay and the extra cost, born by the hospital and the social security, linked to complications, incurring after major surgical procedures. MATERIAL AND METHODS: Study based on the data from 13 Belgian hospitals for the year 2012. Complications were extracted through medical discharge summaries. The cost born by the social security was assessed on the basis of the billing data, hospital cost are taken from cost accounting studies. RESULTS: The rate of complication for all the hospitals is 6.6%. About 30.3% of inpatient stays having a major or extreme severity of index had a complication during the stay, 1.8% of stays with a minor or moderate severity of index had a complication. The extra length of stay is 19.38 days when the stay has had a complication (p < 0.001). The additional mean cost borne from the hospital perspective is €21 353.07 and €8 026.65 for the social security. This additional mean cost varies greatly from one hospital to another. DISCUSSION/CONCLUSION: The present study has shown that the actual financing do not cover real hospital costs in the field of major surgical procedures having caused complications. Results should encourage Belgian authorities to propose and finance preventive measures in order to reduce these complications, which represent major economic impacts, not only for authorities but also for hospitals.

Observation-Based Estimates of Global Glacier Mass Change and Its Contribution to Sea-Level Change.

Glaciers have strongly contributed to sea-level rise during the past century and will continue to be an important part of the sea-level budget during the twenty-first century. Here, we review the progress in estimating global glacier mass change from in situ measurements of mass and length changes, remote sensing methods, and mass balance modeling driven by climate observations. For the period before the onset of satellite observations, different strategies to overcome the uncertainty associated with monitoring only a small sample of the world's glaciers have been developed. These methods now yield estimates generally reconcilable with each other within their respective uncertainty margins. Whereas this is also the case for the recent decades, the greatly increased number of estimates obtained from remote sensing reveals that gravimetry-based methods typically arrive at lower mass loss estimates than the other methods. We suggest that strategies for better interconnecting the different methods are needed to ensure progress and to increase the temporal and spatial detail of reliable glacier mass change estimates.

Costs associated with hospital-acquired bacteraemia in a Belgian hospital.

Studies from around the world have shown that hospital-acquired infections increase the costs of medical care due to prolongation of hospital stay, and increased morbidity and mortality. The aim of this study was to determine the extra costs associated with hospital-acquired bacteraemias in a Belgian hospital in 2001 using administrative databases and, in particular, coded discharge data. The incidence was 6.6 per 10000 patient days. Patients with a hospital-acquired bacteraemia experienced a significantly longer stay (average 21.1 days, P<0.001), a significantly higher mortality (average 32.2%, P<0.01), and cost significantly more (average 12853 euro, P<0.001) than similar patients without bacteraemia. At present, the Belgian healthcare system covers most extra costs; however, in the future, these outcomes of hospital-acquired bacteraemia will not be funded and prevention will be a major concern for hospital management.

[Immune reconstitution syndrome and mycobacterial disease during highly active antiretroviral therapy. Retrospective study of six cases]. / Reconstitution immunitaire et infections à mycobactéries sous traitement antirétroviral. Etude rétrospective de 6 observations.

INTRODUCTION: Soon after starting highly active antiretroviral therapy (HAART), some patients experience clinical deterioration due to the reactivation of their immune system. Mycobacteria are the principal agents complicating this immune reconstitution period. CASES: A retrospective examination of patients with mycobacterial disease before or shortly after beginning HAART at Grenoble University Hospital from January 2001 through July 2004 identified six subjects (among 650 outpatients per year) with a new or aggravated mycobacterial disease after starting HAART. Clinical manifestations were: adenopathy (4/6), hyperthermia (3/6), thoracic pain (2/6), abscess (2/6), and neurological deterioration (1/6). DISCUSSION: Severely immunosuppressed patients who begin HAART may reactivate or aggravate a mycobacterial disease such as tuberculosis. In such cases, current recommendations call for continuing HAART, beginning or continuing the antimycobacterial therapy, and considering corticosteroids on a case-by-case basis. For patients with AIDS, opportunistic infections that might be reactivated should be actively sought before HAART.

[Clinical case of the month. Rendu-Osler-Weber disease: a rare case of stroke in the young]. / Le cas clinique du mois. La maladie de Rendu-Osler : une cause rare d'AVC ischémique chez un sujet jeune.

Rendu-Osler disease or hereditary hemorragic telangiectasia is a group of autosomal dominant diseases characterized by angiodysplasic lesions in the skin, mucous membranes and viscera with risks of recurrent bleedings. Neurological complications have been described in 10-30% of these patients, most often hemorrhagic or septic. More exceptionally, ischemic strokes occur in these patients, particularly if they have pulmonary arteriovenous malformations. We report the observation of a 25 year old man who developed a latero-protuberantial stroke. The explorations revealed pulmonary AV malformations and nasal telangiectasias that led to the diagnostic of Rendu-Osler disease. This affection should be considered as a potential cause of cerebral ischemic attack, particularly in young patients without risk factors.

Impact of protease inhibitors on AIDS-defining events and hospitalizations in 10 French AIDS reference centres. Fédération National des Centres de Lutte contre le SIDA.

OBJECTIVE: To assess the clinical and economic consequences of the use of protease inhibitors in the treatment of HIV infection. DESIGN: Multicentric, observational, retrospective cohort study. SETTING: Ten AIDS reference centres in France. PATIENTS: All patients followed in each centre from September 1995 through October 1996. MAIN OUTCOME MEASURES: AIDS-defining events, death, health-care resources use, administration of antiretroviral therapy. RESULTS: Data from 7749 patients in 10 centres showed a drop in hospitalization days by 35%, new AIDS cases by 35%, and deaths by 46%. In the same period, the proportion of patients receiving antiretrovirals rose from 36 to 53% including highly active antiretroviral therapy (HAART), which rose from 0.3 to 18%. Overall cost evaluation showed a slight increase of monthly treatment cost of US$ 12 per patient. Comparison of the three centres that used HAART earliest to the three centres that used it latest showed a clear benefit to early HAART with a drop in hospitalization days by 41%, new AIDS cases by 41% and deaths by 69%. The proportion of patients with HAART rose to 27% and monthly health-care cost decreased by US$ 248852 (i.e., by US$ 101 per patient per month). Late prescribing centres experienced a less marked effect with a drop in hospitalization days by 22%, new AIDS cases by 31%, and deaths by 32.5%. Proportion of patients with HAART rose to 12% and monthly health-care costs increased by US$ 113578 (i.e., by US$ 38 per patient per month). CONCLUSIONS: This study supports the extensive use of HAART in HIV-infected patients.

Sexually dimorphic expression of calcitonin gene-related peptide (CGRP) immunoreactivity by rat mediobasal hypothalamic neurons.

Although the hypothalamic arcuate nucleus is a sexually dimorphic region of the rat brain, there are no reports of sex differences in the number of neurons containing specific neuropeptides within this structure. As cells synthesizing calcitonin gene-related peptide (CGRP) have been shown to exhibit sex differences in other steroid-receptive regions of the rat brain, we examined whether the CGRP-immunoreactive cells located in the mediobasal hypothalamus may also be sexually dimorphic. Immunostaining of sections from male and female colchicine-treated rats revealed a small population of CGRP-immunoreactive cells distributed throughout the arcuate nucleus. Immunoreactive cells were also detected in the lateral hypothalamic perifornical region, dorsomedial, posterior periventricular and ventral tuberomammillary nuclei, and zona incerta. Cell count analysis revealed approximately twice as many CGRP-immunoreactive cell profiles in the rostral (P < 0.01), middle (P < 0.001), and caudal (P < 0.01) thirds of the arcuate nucleus of male rats compared with females. A significant sex difference in immunoreactive cell numbers (male > female) was also detected within the caudal dorsomedial nucleus (P < 0.05) but not in the posterior periventricular nucleus, perifornical region and zona incerta. Although fibers immunoreactive for CGRP were identified in low density throughout the mediobasal hypothalamus, only female rats displayed prominent fiber staining in the periventricular region. Double-labelling immunofluorescence experiments revealed that the CGRP-immunoreactive cells within the zona incerta, but not the hypothalamus, were also immunoreactive for tyrosine hydroxylase; at least 60% of the A13 dopaminergic neurons co-express CGRP. These results provide evidence that sex differences exist in the number of specific neuropeptide-synthesizing cells within the hypothalamic arcuate nucleus and provide further examples of cell populations expressing CGRP immunoreactivity in a sexually dimorphic manner.

Trimethoprim-sulfamethoxazole versus aerosolized pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia: a prospective, randomized, controlled clinical trial. LFPMI Study Group. Ligue Française de Prévention des Maladies Infectieuses.

The objective was to compare the efficacy and tolerance of monthly aerosolized pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) to prevent the first episode of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. In an open, prospective, randomized multicentric clinical trial, HIV-infected patients (n = 214) with CD4 cell counts < 200/mm3 or 20% without a history of PCP or cerebral toxoplasmosis were randomized to receive for at least 2 years aerosolized pentamidine (300 mg monthly) or low-dose daily TMP-SMX (400-80 mg). The mean follow-up was 578 days. The two groups (except for gender) were homogeneous for age, risk group for HIV infection, initial CD4+ lymphocyte count, and mean follow-up. The PCP rate per year of observation using an intent-to-treat analysis was 3.1% and 1.3% in the groups treated with pentamidine and TMP-SMX, respectively (p > 0.05). Moderate or severe clinical and biological side effects were observed in five patients on pentamidine and 33 on TMP-SMX (p < 0.05). Nineteen episodes of cerebral toxoplasmosis were diagnosed during the study. The analysis showed no significant difference in time of development of toxoplasmosis, but only one patient was actually treated with TMP-SMX. Survival was not significantly different in the two groups. Low-dose daily TMP-SMX or monthly aerosolized pentamidine effectively prevented a first episode of PCP in HIV-infected patients, but aerosolized pentamidine was better tolerated. However, TMP-SMX is less costly and should have a preventive effect for toxoplasmosis.

Trimetazidine European Multicenter Study versus propranolol in stable angina pectoris: contribution of Holter electrocardiographic ambulatory monitoring.

The major objective of the Trimetazidine European Multicenter Study (TEMS) was to compare in a double-blind trial the anti-ischemic effects of trimetazidine (20 mg 3 times daily) with those of propranolol (40 mg 3 times daily). The inclusion criteria were based on an abnormal response to a multistage exercise test. After 3 months of treatment the improvements noted in all exercise testing data were similar in the trimetazidine and propranolol groups; similar data were obtained for the grades and severity of anginal attacks during daily life (from patient diaries). A 24-hour Holter monitoring was performed at entry and at the end of the study, but an abnormal Holter monitoring (1-mm ST-segment depression during at least 1 minute) was not an inclusion criterion. This explains why at entry only 50% of the patients in both groups had an abnormal Holter recording. After 3 months of treatment, there were no significant differences between the 2 groups, but we observed a trend toward a decrease in ambulatory ischemia in the trimetazidine group and a trend toward an increase in ambulatory ischemia in the propranolol group. These data in the propranolol group are in total disagreement with the available literature on beta blockers, which was due to a totally erratic behavior pattern in 2 patients in the propranolol group. When we excluded these 2 erratic cases from the propranolol group and extended our analysis to all available paired comparisons (day -14 to day 30 and day 0 to day 90), we were able to compare 44 and 60 observations, both off therapy and on either propranolol or trimetazidine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

HIV-1 in blood monocytes: frequency of detection of proviral DNA using PCR and comparison with the total CD4 count.

In vivo infection of monocytes/macrophages by the human immunodeficiency virus (HIV) has been investigated in many studies since these cells were suggested to provide a reservoir for the virus. In this study, we wanted to find out whether HIV provirus could be detected in circulating monocytes and whether it could be compared with the provirus found in T lymphocytes (T-Ly). Twenty-one seropositive subjects were studied. The amplification method (PCR) was used with three different primer pairs (in gag, env, and long terminal repeat regions of the viral genome) to detect the HIV-1 genome in monocytes and T-Ly separated by an immunomagnetic isolation technique. Of 21 monocyte samples, 13 (61.9%) were positive with at least one primer pair. Furthermore, the provirus harboured in 9 of those 13 monocyte-positive samples differed, with respect to pattern of primer response, from the provirus found in T-Ly. When comparing primer responses of monocytes and T-Ly, most of the differences were found to have occurred with the env primers (8 of 9 cases). Dilution experiments with the 8 E5 cell line revealed that 9 of 12 T-Ly contained 15-150 HIV DNA copies per 150,000 cells while 8 of 11 positive monocytes contained less than 15 copies. However, monocyte samples from two asymptomatic individuals and an AIDS patient showed high levels of HIV DNA, comparable to those obtained in T-Ly. Finally, it was also found that the monocyte-positive subjects were more immunosuppressed than the negative ones, as shown by the total CD4 count of both groups (means of 269 T4/mm3 and 573 T4/mm3, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Change in transaminases in hepatitis C virus- and HIV-coinfected patients after highly active antiretroviral therapy: differences between complete and partial virologic responders?

Patients with HIV and hepatitis C virus (HCV) coinfection have more severe hepatitis-related disease than do patients with HCV infection alone. Highly active antiretroviral therapy (HAART) with protease inhibitor appears to restore pathogen-specific immune responses, especially in patients with persistent undetectable HIV viral load. To evaluate the potent impact of immune restoration induced by HAART on the course of HCV-related disease, HCV viremia and levels of transaminases were compared between two groups of patients: 10 HIV/HCV-coinfected patients with persistently undetectable HIV viremia (group A) and 12 HIV/HCV-coinfected patients with persistent detectable HIV viremia. No difference was detected in HCV viral load in either group. An increase in transaminases was found only in patients with persistent undetectable HIV viral load, which was correlated with the increase in CD8+ T cells. This may suggest that the restoration of CD8+ T cell cytotoxicity could lead to an enhancement of hepatitis C-related disease in HCV/HIV-coinfected patients receiving HAART.