Attributable mortality due to nosocomial sepsis in Brazilian hospitals: a case-control study.

BACKGROUND: Nosocomial sepsis is a major healthcare issue, but there are few data on estimates of its attributable mortality. We aimed to estimate attributable mortality fraction (AF) due to nosocomial sepsis. METHODS: Matched 1:1 case-control study in 37 hospitals in Brazil. Hospitalized patients in participating hospitals were included. Cases were hospital non-survivors and controls were hospital survivors, which were matched by admission type and date of discharge. Exposure was defined as occurrence of nosocomial sepsis, defined as antibiotic prescription plus presence of organ dysfunction attributed to sepsis without an alternative reason for organ failure; alternative definitions were explored. Main outcome measurement was nosocomial sepsis-attributable fractions, estimated using inversed-weight probabilities methods using generalized mixed model considering time-dependency of sepsis occurrence. RESULTS: 3588 patients from 37 hospitals were included. Mean age was 63 years and 48.8% were female at birth. 470 sepsis episodes occurred in 388 patients (311 in cases and 77 in control group), with pneumonia being the most common source of infection (44.3%). Average AF for sepsis mortality was 0.076 (95% CI 0.068-0.084) for medical admissions; 0.043 (95% CI 0.032-0.055) for elective surgical admissions; and 0.036 (95% CI 0.017-0.055) for emergency surgeries. In a time-dependent analysis, AF for sepsis rose linearly for medical admissions, reaching close to 0.12 on day 28; AF plateaued earlier for other admission types (0.04 for elective surgery and 0.07 for urgent surgery). Alternative sepsis definitions yield different estimates. CONCLUSION: The impact of nosocomial sepsis on outcome is more pronounced in medical admissions and tends to increase over time. The results, however, are sensitive to sepsis definitions.

Does arthroscopic assistance improve reduction in distal articular radius fracture? A retrospective comparative study using a blind CT assessment.

INTRODUCTION: The objective of this study was to compare the articular reduction in two groups of patients with a distal articular radius fracture who underwent surgery with versus without arthroscopic assistance. The initial hypothesis of this study is that arthroscopic assistance does not improve reduction in distal articular radius fractures. METHODS: The study was retrospective (1/04/2014-01/04/2017) and included 41 patients: 23 had arthroscopically assisted osteosynthesis, and 18 had not. All patients included had CT before and 3 months after surgery. All radiographic and CT measurements were retrospectively taken by an independent radiologist who did not know which operative technique was performed. Secondary judgement criteria were clinical analysis at 1-year follow-up and tourniquet time. We also reported all soft tissue injuries diagnosed and repaired and postoperative complications. RESULTS: At the third month, articular step was 0.91 ± 1.25 mm (arthroscopy) and 1.41 ± 1.68 mm (no arthroscopy), without statistical difference (p = 0.3756). No difference was found for articular gap between the two groups [arthroscopy (0.55 ± 1.04 mm), (no arthroscopy (0.82 ± 1.54 mm)] (p = 0.8574). Except for the tourniquet time, clinical results at 1-year follow-up were not different. One patient of each group had a scapholunate pinning, and 6 patients of the arthroscopy group had a TFCC 1B injury, which was repaired. CONCLUSION: This study did not demonstrate that arthroscopic assistance improves step and gap reduction of articular distal radius fracture, confirming initial hypothesis and recent literature data. LEVEL OF EVIDENCE: Retrospective, III.

Extremely premature infants: How does death in the delivery room influence mortality rates in two level 3 centers in France?

OBJECTIVES: Mortality rates of very preterm infants may vary considerably between healthcare facilities depending on the neonates' place of inclusion in the cohort study. The objective of this study was to compare the mortality rates of live-born extremely preterm neonates observed in two French tertiary referral hospitals, taking into account the occurrence of neonatal death both in the delivery room and in the neonatal intensive care unit (NICU). METHODS: Retrospective observational study including all pregnancy terminations, stillbirths and live-born infants within a 22- to 26-week 0/6 gestational age range was registered by two French level 3 university centers between 2009 and 2013. The mortality rates were compared between the two centers according to two places of inclusion: either the delivery room or the NICU. RESULTS: A total of 344 infants were born at center A and 160 infants were born at center B. Among the live-born neonates, the rates of neonatal death were similar in center A (54/125, 43.2%) and center B (33/69, 47.8%; P=0.54). However, neonatal death occurred significantly more often in the delivery room at center A (31/54, 57.4%) than at center B (6/33, 18.2%; P<0.001). Finally, the neonatal death rate of live-born very preterm neonates admitted to the NICU was significantly lower in center A (25/94, 26.6%) than in center B (27/63, 42.9%; P=0.03). CONCLUSIONS: This study points out how the inclusion of deaths in the delivery room when comparing neonatal death rates can lead to a substantial bias in benchmarking studies. Center A and center B each endorsed one of the two models of preferential place of neonatal death (delivery room or NICU) detailed in European studies. The reasons behind the two different models and their impact on how parents perceive supporting their neonate need further investigation.

Claudin-1, miR-122 and apolipoprotein E transductions improve the permissivity of SNU-182, SNU-398 and SNU-449 hepatoma cells to hepatitis C virus.

Hepatitis C virus (HCV) is a human hepatotropic virus, but many hepatoma cell lines are not permissive to this virus. In a previous study, we observed that SNU-182, SNU-398 and SNU-449 hepatoma cell lines were nonpermissive to HCV. To understand the nonpermissivity, we evaluated the ability of each cell line to support the different steps of HCV life cycle (entry, replication and production of infectious particles). Using retroviral pseudoparticles pseudotyped with HCV envelope proteins and recombinant HCV produced in cell culture, we observed that low level or absence of claudin-1 (CLDN1) expression limited the viral entry process in SNU-182 and SNU-398 cells, respectively. Our results also showed that supplementation of the three cell lines with miR-122 partly restored the replication of a JFH1 HCV replicon. Finally, we observed that expression of apolipoprotein E (ApoE) was very low or undetectable in the three cell lines and that its ectopic expression permits the production of infectious viral particles in SNU-182 and SNU-398 cells but not in SNU-449 cells. Nevertheless, the supplementation of SNU-182, SNU-398 and SNU-449 cells with CLDN1, miR-122 and ApoE was not sufficient to render these cells as permissive as HuH-7 cells. Thus, these cell lines could serve as cell culture models for functional studies on the role of CLDN1, miR-122 and ApoE in HCV life cycle but also for the identification of new restriction and/or dependency host factors essential for HCV infection.

Management of acute exacerbations of chronic obstructive pulmonary disease (COPD). Guidelines from the Société de pneumologie de langue française (summary).

Chronic obstructive pulmonary disease (COPD) is the chronic respiratory disease with the most important burden on public health in terms of morbidity, mortality and health costs. For patients, COPD is a major source of disability because of dyspnea, restriction in daily activities, exacerbation, risk of chronic respiratory failure and extra-respiratory systemic organ disorders. The previous French Language Respiratory Society (SPLF) guidelines on COPD exacerbations were published in 2003. Using the GRADE methodology, the present document reviews the current knowledge on COPD exacerbation through 4 specific outlines: (1) epidemiology, (2) clinical evaluation, (3) therapeutic management and (4) prevention. Specific aspects of outpatients and inpatients care are discussed, especially regarding assessment of exacerbation severity and pharmacological approach.

Management of acute exacerbations of chronic obstructive pulmonary disease (COPD). Guidelines from the Société de pneumologie de langue française / Prise en charge des exacerbations de la bronchopneumopathie chronique obstructive (BPCO). Recommandations de la Société de pneumologie de langue française

Chronic obstructive pulmonary disease (COPD) is the chronic respiratory disease with the most important burden on public health in terms of morbidity, mortality and health costs. For patients, COPD is a major source of disability because of dyspnea, restriction in daily activities, exacerbation, risk of chronic respiratory failure and extra-respiratory systemic organ disorders. The previous French Language Respiratory Society (SPLF) guidelines on COPD exacerbations were published in 2003. Using the GRADE methodology, the present document reviews the current knowledge on COPD exacerbation through 4 specific outlines: (1) epidemiology, (2) clinical evaluation, (3) therapeutic management and (4) prevention. Specific aspects of outpatients and inpatients care are discussed, especially regarding assessment of exacerbation severity and pharmacological approach.(AU)

La bronchopneumopathie chronique obstructive (BPCO) est la maladie respiratoire chronique dont le poids sur la santé publique est le plus grand par sa morbidité, sa mortalité et les dépenses de santé qu'elle induit. Pour les individus atteints, la BPCO est une source majeure de handicap du fait de la dyspnée, de la limitation d'activité, des exacerbations, du risque d'insuffisance respiratoire chronique et des manifestations extra-respiratoires qu'elle entraîne. Les précédentes recommandations de la Société de pneumologie de langue française (SPLF) sur la prise en charge des exacerbations BPCO date de 2003. Se fondant sur une méthodologie adaptée de GRADE, le présent document propose une actualisation de la question des exacerbations de BPCO en développant un argumentaire couvrant quatre champs d'investigation : (1) épidémiologie, (2) évaluation clinique, (3) prise en charge thérapeutique et (4) prévention. Les modalités spécifiques de la prise en charge hospitalière et ambulatoire y sont discutées, particulièrement les aspects relevant de l'évaluation de la sévérité de l'exacerbation et de la prise en charge pharmacologique.(AU)

[Termination of pregnancy without feticide: A French national survey]. / L'interruption médicale de grossesse sans fœticide : une enquête nationale.

PURPOSE: Termination of pregnancy without feticide (TOPWF) is poorly known in France and far less practiced than palliative care after term birth of a child having a lethal pathology. Few teams consider it and its practice remains confidential. This survey tries to describe it. MATERIAL AND METHODS: A national survey was realized in 2014 using a questionnaire sent to 50 centers of prenatal diagnosis depending on a perinatal diagnosis center in France. RESULTS: Thirty-one centers answered the questionnaire. Seven teams shared their experience of TOPWF after 22-24 weeks gestation (WG). This practice concerned fetuses affected by "lethal" pathologies. The absence of feticide followed a parental request or a proposal of the medical team, after individual discussion in a multidisciplinary meeting. All the children born alive after TOPWF benefited of palliative care. The 24 other centers having answered our investigation performed systematically the feticide beyond 22-24 WG. They so wished "to protect" the fetus, the parents and the nursing team. A majority of these teams faced parental demands of abstention of feticide but few of them answered it favorably. CONCLUSION: A robust "palliative culture" seems essential to allow the nursing team to consider the development of TOPWF.

Ofatumumab in refractory chronic lymphocytic leukemia: experience through the French early access program.

BACKGROUND: The Autorisation Temporaire d'Utilisation (ATU) is an early access program available in France for drugs aimed at treating severe diseases not yet covered by a marketing authorization, for patients without any other therapeutic option and who cannot be included in a clinical trial. PATIENTS AND METHODS: This report presents the use of single-agent ofatumumab in 30 patients with advanced chronic lymphocytic leukemia (CLL) in the French ATU program. RESULTS: These very-high-risk patients had received multiple previous treatments (median = 6), and most had disease that was fludarabine-refractory or alemtuzumab-refractory (or both) or was unsuitable for alemtuzumab treatment. In the intent-to-treat analysis, the overall response rate was 47% (4 of 30, complete response; 10 of 30, partial response). Of 13 patients with 17p deletion, 6 displayed response to ofatumumab, including 2 complete responses. Treatment was well tolerated, with 17 grade 3 or 4 adverse events; 4 cases of grade 3 or 4 infusion reactions were reported, with favorable immediate outcome. Among nonhematologic complications, infections were the most frequent. CONCLUSION: The results confirm the efficacy and acceptable tolerability profile of ofatumumab as a single agent in severely ill patients with CLL. Attention should be paid to possible early infusion reactions to ofatumumab, as well as to the risk of infection.

[Palliative care for patients with heart failure]. / Soins palliatifs chez les patients en insuffisance cardiaque terminale.

PURPOSE: Heart failure is a common disease and its progression to end-stage heart failure is responsible of high mortality. The aim of this retrospective study was to assess the access to integrated palliative care to the usual management, 6 months prior to their death, and especially during the last hospitalization. PATIENTS AND METHODS: A retrospective study was performed in patients who died of heart failure in 2009 in two hospitals. The analysis was performed on 20 cases of each institution. The records of consecutive patients were included in an anti-chronological order from 31st December 2009. RESULTS: For their last hospitalization, 37 patients (93%) were hospitalized in emergency. Within 3 days prior to death, the most frequent symptoms were dyspnea (n=33, 82%), and pain (n=30, 75%). Therapeutic most frequently used were oxygen (n=31, 77%) and analgesics (n=30, 75%). No patient was seen by a psychologist. The decision to limit treatment for comfort care was reported for 24 patients (60%) and the median of the average time between the decision and death was 2 days (Q1-Q3, 1-5 days). CONCLUSION: Patients with terminal heart failure have many symptoms often requiring multidisciplinary care. This type of study relating practices shows that there is still a lot to do to integrate palliative care in the usual management of patients with heart failure.

[Palliative care for patients with COPD: a challenge]. / La BPCO : parent pauvre des soins palliatifs ?

INTRODUCTION: The aim of our study was to examine the practices and performance of a team working in a respiratory unit concerning the palliative care of patients with COPD, in a group of patients who died in hospital as a result of their disease. METHODOLOGY: The first step was focused on those patients who died in the respiratory care unit of the General Hospital of Saint-Nazaire during the year 2008 and who received end-of-life care, and the reasons for their death. In the second step, we selected and analysed retrospectively the records of patients who died from COPD. In the third step semi-directive interviews were held with a sample of nine care workers who were judged to be representative of the staff working in the respiratory ward of Saint-Nazaire Hospital. The interviews consisted of seven questions related to palliative practices and professional experiences acquired during the care of patients with COPD. RESULTS: In a population of 51 patients who received end-of-life care during the year 2008, 34 were referred on account of lung cancer and only one was referred for COPD. Bronchial carcinoma was the main cause of death (36 cases) then COPD (16 cases) in a total of 92 deaths (2008). Retrospective analysis of the records of patients who died from COPD showed a limitation of care in 43% of cases, midazolam induced sedation in 43%, treatment with morphine in 37%, support for the family or relatives in 62% and some anticipated decisions in 6%. Analysis of the interviews showed that the subject of death is rarely or never discussed with these patients in contrast to patients dying from bronchial cancer. CONCLUSION: The practices of a respiratory team concerning palliative care in COPD patients appear to be limited to end-of-life care. This clearly reflects a need for palliative care education in workers of respiratory care units in order to deliver a global palliative approach at an earlier stage in the care of COPD patients and to improve communication concerning end-of-life treatments.

Genetic recombination of the hepatitis C virus: clinical implications.

Genetic recombination is a well-known feature of RNA viruses that plays a significant role in their evolution. Although recombination is well documented for Flaviviridae family viruses, the first natural recombinant strain of hepatitis C virus (HCV) was identified as recently as 2002. Since then, a few other natural inter-genotypic, intra-genotypic and intra-subtype recombinant HCV strains have been described. However, the frequency of recombination may have been underestimated because not all known HCV recombinants are screened for in routine practice. Furthermore, the choice of treatment regimen and its predictive outcome remain problematic as the therapeutic strategy for HCV infection is genotype dependent. HCV recombination also raises many questions concerning its mechanisms and effects on the epidemiological and physiopathological features of the virus. This review provides an update on recombinant HCV strains, the process that gives rise to recombinants and clinical implications of recombination.

[Pain management, let us be simple but efficient]. / Prise en charge de la douleur, soyons simple mais efficace.

The occurrence of pain during the course of bronchial carcinoma is nearly inescapable and often constitutes the main symptom for patients and those close to them. While pain control is held to be a priority of care in cancerology in the future, this goal is not always reached due to insufficient implementation of recommendations, however widely accessible. Our aim is to present the different aspects of pain treatment through the details of both pharmacological and nonpharmacological means.

[Chronic urticaria]. / Urticaire chronique.

Chronic urticaria (CU) is a common disease of unknown origin. Its impact on the quality of life is significant. Antibodies to high affinity receptors expressed on mast cells and basophiles (FcepsilonRI) are found in 30% of cases and may be associated with more severe and prolonged symptoms. A wide variety of disorders can be associated with CU. However, in the absence of suggestive signs or symptoms, an extensive workup rarely permits the diagnosis of an underlying pathology. In this case, the work up should be minimal. The newer generation oral anti-histamines represent the first line treatment. In the refractory cases, other drugs may be considered but few controlled studies support their use.

Successful treatment of disseminated Geotrichum capitatum infection with a combination of caspofungin and voriconazole in an immunocompromised patient.

Disseminated Geotrichum capitatum infection is uncommon, and has been reported exclusively in immunocompromised patients. The prognosis is poor with a mortality rate of approximately 50-75%. We report a case of disseminated G. capitatum infection in a severely neutropenic patient who was receiving chemotherapy for acute myeloblastic leukaemia. G. capitatum was isolated from blood cultures, skin lesions, bronchoalveolar lavage fluid, throat swabs and stools. The infection was successfully cured with a combination of voriconazole and caspofungin.

Genetic features of polioviruses isolated in Tunisia, 1991-2006.

BACKGROUND: Genetic characterisation of polioviruses remains highly important even in countries where wild poliovirus circulation has been interrupted. Sequence data on representative wild strains from all geographical regions is required for surveillance purposes and surveillance for vaccine-related isolates with increased potential for transmissibility in humans should continue. OBJECTIVE: To report the genetic characteristics of wild and vaccine-related polioviruses isolated in Tunisia from 1991 to 2006. STUDY DESIGN: Wild isolates were sequenced in the VP1 genomic region and compared to each other. Vaccine-related isolates were assessed for genetic recombination by PCR/RFLP and sequence analysis of the 3D region. Recombinant viruses were assessed for genetic drift in the VP1 region. RESULTS: The VP1 sequences of the last wild isolates, all from serotype3, showed 97.7-98.7% nucleotide homology. Nineteen percent of vaccine-related isolates were vaccine/vaccine intertypic recombinants. No recombinant with non-poliovirus enteroviruses was identified. Mutational differences in the VP1 sequences of recombinant viruses ranged from 0.0% to 0.7% indicating a limited replication period. CONCLUSIONS: This study provides sequence data on wild polioviruses from Tunisia/North Africa and shows that in countries with continuous high vaccine coverage transmission of vaccine-related polioviruses is time-limited.