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Biomedical subjects

M Danis

Publications and source records attributed to M Danis.

At least 37 records · Page 2Linked to original sources

End-of-life care in the intensive care unit: where are we now?

A growing body of evidence and experience has effaced what were once thought to be clear distinctions between "critical illness" and "terminal illness" and has exposed the problems of postponing palliative care for intensive care patients until death is obviously imminent. Integration of palliative care as a component of comprehensive intensive care is now seen as more appropriate for all critically ill patients, including those pursuing aggressive treatments to prolong life. At present, however, data on which to base practice in this integrated model remain insufficient, and forces of the healthcare economy and other factors may constrain its application. The purpose of this article is to map where we are now in seeking to improve palliative care in the intensive care unit. We review existing evidence, which suggests that both symptom management and communication about preferences and goals of care warrant improvement and that prevailing practices for limitation of life-sustaining treatments are inconsistent and possibly irrational. We also address the need for assessment tools for research and quality improvement. We discuss recent initiatives and ongoing obstacles. Finally, we identify areas for further exploration and suggest guiding principles.

Communication↗

Conflict resolution at the end of life.

OBJECTIVE: Limited empirical research has examined how decisions are made when the preferences of terminally ill patients conflict with physicians' recommendations. This study sought to investigate physicians' strategies for resolving conflicts with dying patients. DESIGN: Cross-sectional, qualitative interviews. SUBJECTS: Subjects were 158 physicians caring for at least one terminally ill patient. SETTING: University medical center. MEASUREMENTS AND MAIN RESULTS: We analyzed physicians' responses to the open-ended interview questions, "How do you handle a situation when a patient wants a treatment that you believe does not provide any benefit?" and "How do you handle a situation when a patient does not want a treatment you think would be beneficial?" For patient requests of nonbeneficial treatments, physicians reported the following as important: negotiating with and educating patients (71%), deferring to patient requests for benign or uncomplicated treatments (34%), convincing patients to forgo treatments (33%), refusing patient requests for nonbeneficial treatment (22%), using family influence (16%), not offering futile treatments (13%), and referring to other physicians for disputed care (9%). Potential harm (23%) and cost of treatment (18%) were reasons cited for withholding treatments. In response to patient refusals of beneficial treatments, physicians report the following as important: negotiating with patients (59%), convincing patients to receive treatment (41%), assessing patient competence (32%), using family influence (27%), and referring to other physicians (21%). CONCLUSIONS: Physicians vary in the communication and negotiation strategies they use when their medical judgment conflicts with dying patients' preferences. Medical ethicists could play a greater role in teaching ethically important communication skills. Physicians providing care at the end of life report strategies for respecting patients that reflect graduated degrees of accommodation tailored to the costliness and riskiness of requests; they are most accepting of patient requests for benign, technically easy, inexpensive, and medically effective treatments.

Adult↗

One-step purification of Enterocytozoon bieneusi spores from human stools by immunoaffinity expanded-bed adsorption.

An original, reliable, and reproducible method for the purification of Enterocytozoon bieneusi spores from human stools is described. We recently reported the production of a species-specific monoclonal antibody (MAb) 6E52D9 immunoglobulin G2a (IgG2a) raised against the exospore of E. bieneusi spore walls. The MAb was used as a ligand to develop an immunoaffinity matrix. The mouse IgG2a MAb was bound directly to a Streamline rProtein A adsorbent, used for expanded-bed adsorption of immunoglobulins, for optimal spatial orientation of the antibody and maximum binding efficiency of the antigen. The complex was then cross-linked covalently using dimethyl pimelimidate dihydrochloride. After incubation of the immunoaffinity matrix with filtered stool samples containing numerous E. bieneusi spores and before elution with 6 M guanidine HCl, the expansion of the adsorbent bed eliminated all the fecal contaminants. The presence of spores in the elution fractions was determined by an indirect immunofluorescence antibody test (IFAT). E. bieneusi spores were found in the elution fraction in all four experiments and were still highly antigenic as indicated by IFAT. Smears examined by light microscopy contained very clean spores with no fecal debris or background bacterial and fungal contaminants. However, spore recovery rates were relatively low: an average of 10(7) spores were purified per run. This technique for isolating E. bieneusi spores directly from human stool samples with a high degree of purity opens up new approaches for studying this parasite.

AIDS-Related Opportunistic Infections↗

What triggers requests for ethics consultations?

OBJECTIVES: While clinical practice is complicated by many ethical dilemmas, clinicians do not often request ethics consultations. We therefore investigated what triggers clinicians' requests for ethics consultation. DESIGN: Cross-sectional telephone survey. SETTING: Internal medicine practices throughout the United States. PARTICIPANTS: Randomly selected physicians practising in internal medicine, oncology and critical care. MAIN MEASUREMENTS: Socio-demographic characteristics, training in medicine and ethics, and practice characteristics; types of ethical problems that prompt requests for consultation, and factors triggering consultation requests. RESULTS: One hundred and ninety of 344 responding physicians (55%) reported requesting ethics consultations. Physicians most commonly reported requesting ethics consultations for ethical dilemmas related to end-of-life decision making, patient autonomy issues, and conflict. The most common triggers that led to consultation requests were: 1) wanting help resolving a conflict; 2) wanting assistance interacting with a difficult family, patient, or surrogate; 3) wanting help making a decision or planning care, and 4) emotional triggers. Physicians who were ethnically in the minority, practised in communities under 500,000 population, or who were trained in the US were more likely to request consultations prompted by conflict. CONCLUSIONS: Conflicts and other emotionally charged concerns triggers consultation requests more commonly than other cognitively based concerns. Ethicists need to be prepared to mediate conflicts and handle sometimes difficult emotional situations when consulting. The data suggest that ethics consultants might serve clinicians well by consulting on a more proactive basis to avoid conflicts and by educating clinicians to develop mediation skills.

Attitude of Health Personnel↗

Neurologic sequelae after severe falciparum malaria in adult travelers.

Severe falciparum malaria usually occurs in nonimmune patients, namely children in endemic areas or travelers returning from tropical areas. It generally has one of two outcomes: rapid death or cure without sequelae. Neurologic sequelae have been reported in children but have not been described in detail in adults. The purpose of this study was to determine the clinical spectrum, neuroimaging aspects and long-term outcome of these sequelae. We describe six imported cases of severe malaria with neurologic sequelae in adults, seen in a Parisian university hospital over a 10-year period. The most striking findings were neuropsychological disorders, in particular memory impairment and diffuse white matter damage on magnetic resonance imaging. Only three of the patients had made a full recovery after 6 months.

Adult↗

Cytoadherence characteristics of Plasmodium falciparum isolates in Thailand using an in vitro human lung endothelial cells model.

Using an in vitro model of human lung endothelial cells, we studied different characteristics of Plasmodium falciparum isolates as potential factors for malaria severity in 2 Thai patient groups: 27 with complicated malaria and 42 with uncomplicated malaria. In regard to binding properties, no association existed between cytoadherence and rosette phenotypes (P = 0.1) and hypothrombocytemia increased the cytoadherence level (P = 0.007). Cytoadherence was significantly associated with malaria severity (P = 0.05) in contrast to rosette formation (P = 0.9). Intercellular adhesion molecule-1 and chondroitin-4-sulfate were major receptors of cytoadherence in those with complicated malaria compared with those with uncomplicated malaria (P < 10(-4)). Chondroitin-4-sulfate could act as a putative receptor for malaria complications in non-pregnant women. CD36 was the main receptor in patients with uncomplicated malaria (P < 10(-3)). Vascular cell adhesion molecule-1 and E-selectin played a minor role in 2 groups (P = 0.6). Qinghaosu derivatives were more efficient than other antimalarial drugs, but a positive correlation was observed between the 50% inhibitory concentrations of halofantrine and quinine and the number of adhesive parasitized red blood cells, suggesting their influence on cytoadherence.

Adolescent↗

Neurocysticercosis: utilizing the cystic fluid antigen from Taenia solium metacestodes for diagnosis by IgG-ELISA.

Cystic fluid, which has antigenic properties of whole Taenia solium cysticerci, was used to discriminate neurocysticercosis cases and other parasitic infections, especially helminthiases. Twenty-one neurocysticercosis and several kinds of 22 different parasitic infections, including HIV cases (n=234) evaluated a 90.48% sensitivity and 86.32% specificity of indirect ELISA as follows: a low antigen concentration of 5 microg/ml. serum dilution of 1:400, conjugate dilution of 1:2,000 and a cut-off value of 0.349. Eight different helminthic infections (n = 25); echinococcosis (8/10), gnathostomiasis (6/8), strongyloidiasis (5/14), hookworm infection (1/18), angiostrongyliasis (2/25), opisthorchiasis (1/18), onchocercosis (1/3) and toxocariasis (1/6) were cross-reactive with this antigen. No serum antibody from other brain infections in the study gave a reaction with the antigen. In this study, the cystic fluid antigen gave high sensitivity of the test. However, the antigen contains various antigenic molecules able to bind with antibodies from several of the above helminthic sera, especially echinococcosis and gnathostomiasis. In Thailand, gnathostomiasis is one of the more famous tropical diseases but echinococcosis is quite rare. Cystic fluid antigen should be further investigated for its specific finding in diagnosis.

Animals↗

Community physicians who provide terminal care.

BACKGROUND: Most dying patients are treated by physicians in community practice, yet studies of terminal care rarely include these physicians. OBJECTIVE: To examine the frequency of life-sustaining treatment use and describe what factors influence physicians' treatment decisions in community-based practices. METHODS: Family members and treating physicians for decedents 65 years and older who died of cancer, congestive heart failure, chronic lung disease, cirrhosis, or stroke completed interviews about end-of-life care in community settings. RESULTS: Eighty percent of eligible family and 68.8% of eligible physicians participated (N = 165). Most physicians were trained in primary care and 85.4% were primary care physicians for the decedents. Physicians typically knew the decedent a year or more (68.9%), and 93.3% treated them for at least 1 month before death. In their last month of life, 2.4% of decedents received cardiopulmonary resuscitation, 5.5% received ventilatory support, and 34.1% received hospice care. Family recalled a discussion of treatment options in 78.2% of deaths. Most discussions (72.1%) took place a month or more before death. Place of death, cancer, and having a living will were independent predictors of less aggressive treatment before death. Physicians believed that advanced planning and good relationships were the major determinants of good decision making. CONCLUSIONS: Community physicians use few life-sustaining treatments for dying patients. Treatment decisions are made in the context of long-term primary care relationships, and living wills influence treatment decisions. The choice to remain in community settings with a familiar physician may influence the dying experience.

Advance Care Planning↗

The comparative efficacy and tolerability of CGP 56697 (artemether + lumefantrine) versus halofantrine in the treatment of uncomplicated falciparum malaria in travellers returning from the Tropics to The Netherlands and France.

CGP 56697 (Riamet) is a new oral anti-malarial drug composed of artemether and lumefantrine (benflumetol) which combines the fast, short-acting artemether for rapid parasite clearance with the prolonged action of lumefantrine for intended radical cure. In this double-blind, comparative trial, the efficacy and tolerability of CGP 56697, given as a course of 4 x 4 tablets over 48 h, was compared to halofantrine, given as 3 x 2 tablets over 12 h with a second course 1 week later. Patients (mostly non-immune) with acute, uncomplicated Plasmodium falciparum infection were randomly assigned to either CGP 56697 (n = 51) or halofantrine (n = 52). CGP 56697 proved superior with respect to parasite clearance time (median 32 vs. 48 h, P < 0.001) and parasite reduction at 24 h (median 99.7 vs. 89.6%, P < 0.001) with a non-significant difference in resolution of fever (median 24 vs. 32 h, P = 0.835). However, a 28-day cure rate of 82% was observed for CGP 56697 and 100% for halofantrine. Significant QTc prolongations (> 30 ms) were seen 6-12 h after halofantrine intake but not after CGP 56697 intake. CGP 56697 is an effective, well-tolerated treatment for uncomplicated falciparum malaria but for this dosing regimen the recrudescence rate is unacceptablyhigh (18%). For travellers contracting malaria abroad, we propose a six-dose regimen of CGP 56697 over 3 days.

Adolescent↗

Circulating receptors implicated in the cyto-adherence occurring in severe Plasmodium falciparum malaria in Thailand.

The kinetic profiles of soluble chondroitin-sulphate A (CSA), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin were investigated in 17 patients hospitalized with Plasmodium falciparum malaria. The aim was to see if these circulating adhesion molecules could be considered as markers for the severity of P. falciparum malaria. The levels of all the adhesion molecules were found to be higher in the sera from all the malaria cases, both severe and uncomplicated, than in those from uninfected controls. The elevation in plasma CSA, reported for the first time, was statistically very significant (P = 0.00001). However, when severe cases were compared with the uncomplicated, there were no significant differences in the level of any of the receptors except ICAM-1, which was highest in those with the severe disease (P = 0.01). The absence of any significant correlation between the plasma concentration of CSA and malaria severity indicates that this adhesion molecule could not be used to predict the severity of malaria, although its role in sequestration of the parasites in pregnant women is well established.

Adolescent↗

The microculture tetrazolium assay (MTA): another colorimetric method of testing Plasmodium falciparum chemosensitivity.

Malarial lactate dehydrogenase (LDH), which uses 3-acetyl pyridine adenine dinucleotide as coenzyme in a reaction leading to the formation of pyruvate from L-lactate, may be used to study the susceptibility of Plasmodium falciparum to a drug in vitro. Several methods to determine the activity of this enzyme are available. One, the colorimetric method of Makler and colleagues, was modified slightly, by using sodium-2,3-bis-[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5 - carboxanilide (XTT) and following the reaction by measuring the optical density at 450 nm. Using two, culture-adapted strains of P. falciparum, this LDH assay was compared with the unmodified Makler's assay and with the isotopic microtest based on the incorporation of tritium-labelled hypoxanthine. Fresh, clinical P. falciparum isolates were also tested in the presence of several drugs, including chloroquine, mefloquine, quinine, halofantrine, atovaquone and qinghaosu derivatives. The results of the three assays were correlated for all the drugs tested except atovaquone. The two enzymatic assays are non-radioactive, rapid, reliable, inexpensive to perform and semi-automatic. However, they do require an initial parasitaemia of 2% with a haematocrit of 1.8%.

Animals↗

Incorporating palliative care into critical care education: principles, challenges, and opportunities.

OBJECTIVE: To identify the goals and methods for medical education about end-of-life care in the intensive care unit (ICU). DATA SOURCES AND STUDY SELECTION: A status report on palliative care, a summary report of recent research on palliative care education, articles in the medical literature on end-of-life care and critical care, and expert opinion were considered. DATA EXTRACTION: A working group, including specialists in critical care, palliative care, medical ethics, consumer advocacy, and communications, was convened at the "Medical Education for Care Near the End of Life National Consensus Conference." A modified nominal group process was used to develop a consensus. DATA SYNTHESIS: In the ICU, life and death decisions are often made in a crisis mode or in the face of uncertainty, and may necessitate the withholding and withdrawal of life-supporting technologies. Because critical illness often diminishes the capacity of patients to make decisions, clinicians must often make decisions in conjunction with surrogates, rather than with patients. Discontinuity of care can threaten trusting relationships, and cultural diversity can have a particularly powerful impact on choices for care. In the face of these realities, it is possible and appropriate to give compassionate palliative care to dying patients and their families in the ICU. CONCLUSIONS: Teaching care of the dying in the ICU should emphasize the following: a) the goals of care should guide the use of technology; b) understanding of prognostication and treatment withholding and withdrawal is essential; c) effective communication and trusting relationships are crucial to good care; d) cultural differences should be acknowledged and respected; and e) the delivery of excellent palliative care is appropriate and necessary when patients die in the ICU.

Attitude to Death↗

Development of a Plasmodium PCR for monitoring efficacy of antimalarial treatment.

We report in this work a highly sensitive and nonradioactive PCR method for the detection of the four species of parasite causing human malaria. Plasmodium-specific primers corresponding to the small-subunit rRNA genes of the malaria parasite were used, and a 291-bp fragment was amplified. Our results showed a high specificity for the four human Plasmodium species, and we were able to detect one parasite in 50 microl of whole blood. The responses of 12 patients infected with Plasmodium falciparum to antimalarial therapy were monitored by PCR diagnosis and examination of thick blood film for at least 20 min by an experienced microscopist. For one patient this study allowed early diagnosis of therapeutic failure, confirmed 7 days later by examination of the thick blood film. A total of 134 samples were examined; 94 were positive by PCR, and among these 68 were positive by thick blood film examination. The sensitivity of the thick blood film was 72.3% compared to PCR and 60.7% compared to dot blot hybridization.

Animals↗

Production of monoclonal antibodies directed against the microsporidium Enterocytozoon bieneusi.

Several hybridomas producing antibodies detected by indirect immunofluorescence antibody test (IFAT) were established by fusion of mouse myeloma SP2/O with spleen cells from BALB/c mice immunized against whole spores (protocol 1) or chitinase-treated spores (protocol 2) of Enterocytozoon bieneusi and were cloned twice by limiting dilutions. Two monoclonal antibodies (MAbs), 3B82H2 from protocol 1, isotyped as immunoglobulin M (IgM), and 6E52D9 from protocol 2, isotyped as IgG, were expanded in both ascites and culture. IFAT with the MAbs showed that both MAbs reacted exclusively with the walls of the spores of E. bieneusi, strongly staining the surface of mature spores, and produced titers of greater than 4,096. Immunogold electron microscopy confirmed the specific reactivities of both antibodies. No cross-reaction, either with the spores of the other intestinal microsporidium species Encephalitozoon intestinalis or with yeast cells, bacteria, or any other intestinal parasites, was observed. The MAbs were used to identify E. bieneusi spores in fecal specimens from patients suspected of having intestinal microsporidiosis. The IFAT was validated against standard staining methods (Chromotrope 2R and Uvitex 2B) and PCR. We report here the first description and characterization of two MAbs specific for the spore wall of E. bieneusi. These MAbs have great potential for the demonstration and species determination of E. bieneusi, and their application in immunofluorescence identification of E. bieneusi in stool samples could offer a new diagnostic tool for clinical laboratories.

AIDS-Related Opportunistic Infections↗