Biomedical subjects

S Chevret

Publications and source records attributed to S Chevret.

At least 37 records · Page 2Linked to original sources

PubMed2001

Evaluating treatment strategies in advanced Waldenström macroglobulinemia: use of quality-adjusted survival analysis.

A randomized phase II multicenter clinical trial comparing the efficacy of fludarabine (FAMP) to that of the association of cyclophosphamide, doxorubicin and prednisone (CAP) in 92 patients with Waldenstrom's macroglobulinemia in first relapse or with primarily resistant disease, was conducted on the behalf of the 'Groupe Coopératif Macroglobulinémie'. The main analysis of this study failed to demonstrate a clear cut benefit of FAMP in terms of overall survival (OS), although a significant benefit in terms of time to disease progression and event-free survival (EFS) was noted. In this rare disorder, where few randomized trials have been conducted, we took advantage of this trial to assess treatment differences while integrating quality of life considerations. We thus performed a quality-adjusted survival analysis, using the quality-adjusted time without symptoms or toxicity (Q-TWiST) approach. Four health states differing in terms of quality of life (QoL) were defined, namely treatment-related toxicity, treatment free of toxicity, no treatment or symptoms, and relapse. The average time spent in these health states (TOX, CT, TWiST and REL, respectively) were then weighted by utility coefficients reflecting relative QoL value according to that of TWiST and summed up giving the so-called Q-TWiST. No difference was found between randomized groups in terms of mean CT. Mean TOX in the two groups were similarly close except when considering alopecia as a relevant toxic event. By contrast, mean TWiST was 5.9 months longer in the FAMP group than in the CAP group (P = 0.006). Unsurprisingly, given the absence of difference in OS but the difference in EFS in favor of the FAMP group, mean REL was increased by 6.8 months in the CAP group (P = 0.047). As a result, benefit of FAMP in terms of average Q-TWiST only relied on the value of the utility coefficient attributed to REL (U(REL)), with a significant benefit when UREL ranged from 0 to 0.28, ie in patients undergoing poor QoL after relapse, which is likely.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Virologic and immunologic parameters that predict clinical response of AIDS-associated Kaposi's sarcoma to highly active antiretroviral therapy.

The purpose of the work was to assess the predictive value of biologic factors on the efficacy of highly active antiretroviral therapy alone or combined with chemotherapy on AIDS-associated Kaposi's sarcoma. Twenty-six AIDS-Kaposi's sarcoma patients who started therapy with protease inhibitors were investigated. No baseline chemotherapy was associated with less severe initial clinical status. Median follow-up was 652 d. The main outcome measures were as follows: best Kaposi's sarcoma clinical response; Kaposi's-sarcoma-associated herpesviral load in peripheral blood mononuclear cells using real-time quantitative polymerase chain reaction (non-detectable if less than 100 copies per microg); human immunodeficiency viral charge in plasma (non-detectable if less than 200 copies per ml); and CD4 lymphocyte count. Time to undetectable Kaposi's-sarcoma-associated herpesviral load, time to undetectable human immunodeficiency viral charge, and time to CD4 >or= 150 per microl were also recorded over time, from 2 mo measurements. Patients were staged according to the AIDS Clinical Trials Group-based tumor, immune, systemic staging system criteria. At baseline, Kaposi's sarcoma was progressive for 25 (96%) of the 26 enrolled patients. Complete or partial response to highly active antiretroviral therapy alone or combined with chemotherapy was achieved in 22 patients (85%). Median time to clinical response was estimated at 251 d. Clinical response was faster in patients without chemotherapy at baseline (p = 0.003) as well as in patients not previously treated with reverse transcriptase inhibitors (p = 0.0012). Using univariable analyses, predictive factors of clinical response were undetectable Kaposi's-sarcoma-associated herpesviremia (p = 0.013), undetectable human immunodeficiency viremia (p = 0.03), and relative variation of CD4 lymphocytes (p = 0.004). Using multivariable analysis, undetectable Kaposi's-sarcoma-associated herpesviremia (p = 0.009) and relative variation of CD4 (p = 0.005) were independently selected as having a predictive value for clinical response. Occurrence of nondetection of either Kaposi's-sarcoma-associated herpesvirus or human immunodeficiency virus was not associated with baseline CD4 value. Kaposi's-sarcoma-associated herpesvirus quantitative viral charge is an independent predictive factor of the efficacy of highly active antiretroviral therapy on AIDS-Kaposi's sarcoma. Our results support immune reconstitution as a mechanism of response of Kaposi's sarcoma to highly active antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Results of unrelated umbilical cord blood hematopoietic stem cell transplantation.

The number of umbilical cord blood transplants is increasing worldwide. The purpose of Eurocord is to evaluate the results and to compare the outcome of umbilical cord blood transplants with allogeneic bone marrow transplants. Data have been reported to Eurocord by multiple transplant centers. Close links have been established with the cord blood banks through Netcord. Bone marrow transplant data have been provided by transplant centers and also through the European Group for Blood and Marrow Transplantation (EBMT) and International Bone Marrow Transplant Registries (IBMTR). Eurocord has analyzed the outcome of unrelated umbilical cord blood transplants from 121 transplant centers and 29 countries. The results showed that survival with unrelated mismatched umbilical cord blood transplants was comparable to that with unrelated bone marrow transplants. Engraftment with cord blood was delayed, resulting in an increased incidence of early transplant complications. The incidence of acute and chronic graft-vs.-host disease was reduced with cord blood grafts even in human leukocyte antigen (HLA)-mismatched transplants and in adults. In patients with leukemia, the rate of relapse was similar to the rate of relapse after bone marrow transplant. The overall event-free survival with umbilical cord blood transplantation was not statistically different when compared to bone marrow transplants. This large registry study confirms the potential benefit of using umbilical cord blood hematopoietic stem cells for allogeneic transplants.

Fetal Blood↗

PubMed2001

Routine exploratory thoracentesis in ICU patients with pleural effusions: results of a French questionnaire study.

PURPOSE: The purpose of this study was to report the opinions of intensivists regarding pleural effusions in patients in the intensive care unit (ICU). MATERIALS AND METHODS: Questionnaires were sent to 1,032 intensivists, who were members of the French Society of Critical Care. RESULTS: Four hundred thirty-one questionnaires (41.7%) were returned. Overall, the respondents' estimated the incidence of pleural effusion in ICU patients to be 22.19 +/- 17%, whereas 37 +/- 27% considered that exploratory thoracentesis was likely to determine the cause of the effusion, and 17.36 +/- 16% considered that its results were likely to result in a change in their therapeutic attitude. Sixty-five (15%) physicians, chiefly pulmonologists, performed exploratory thoracentesis routinely (Group 1). Compared with those who did not perform routine thoracentesis (Group 2), they ascribed a higher proportion of pleural effusions to infection (31.3% vs. 13.5%) and were more likely to consider that exploratory thoracentesis had a diagnostic and therapeutic contribution (51.2% vs. 34% and 23% vs. 16%, respectively). In addition to the respiratory medicine subspecialty, the practice of routine exploratory thoracentesis was significantly related to seniority, to the frequency of the suspicion of an infectious cause in the physician's practice, and to his or her appreciation of the risks associated with exploratory thoracentesis. Physicians from Group 1 were also more likely to describe exploratory thoracentesis as a noninvasive procedure. CONCLUSIONS: The beliefs and attitudes of intensivists regarding pleural effusions and exploratory thoracentesis are divergent. This may be due to the lack of precise guidelines on the topic and prompt the design of further studies to establish precisely the epidemiology and causes of pleural effusions in ICU patients.

Attitude of Health Personnel↗

PubMed2001

The tolerance and efficacy of interferon-alpha in haemodialysis patients with HCV infection: a multicentre, prospective study.

BACKGROUND: A prospective multicentre study was initiated in HCV-infected haemodialysis patients to assess the tolerance and efficacy of alpha-2b interferon. METHODS: We had planned to include 120 patients with HCV RNA detectable by polymerase chain reaction (PCR) (Amplicor Roche) and histologically documented chronic hepatitis. The dose of alpha-interferon was 3 million units (MU) three times weekly (TTW), to be reduced to 1.5 MU TTW in case of side-effects. Tolerance was evaluated monthly; virological efficacy was evaluated by PCR. A liver biopsy was performed at month 18 (M18). RESULTS: (a) TOLERANCE: After 37 patients had been included, the study was discontinued by the promoting institution because of severe side-effects requiring that treatment be stopped in 19 patients. The side-effects were: cardiac (4) neuropsychiatric (2), digestive (3), acute necrosis of the graft (1), severe asthenia (9), minor side-effects were observed in 22 patients. A complete 12-month course was completed in 12 patients for the 3 MU TTW dose and in six patients for the 1.5 MU TTW reduced dose. Normal ALT level (OR, 0.16; CI 95%, 0.03-0.89) at inclusion was associated with interruption of treatment (univariate analysis). (b) EFFICACY: Sustained virological response was observed in only seven (18.9%), of the 18 patients who completed the treatment (38%). Increased ALT at inclusion (OR, 1.04; CI 95%, 1.01-1.09) and cumulated doses of interferon (OR, 1.01; CI 95%, 1.004-1.026) were jointly associated with a sustained response, while positive PCR at M2 was strongly predictive of treatment failure. CONCLUSION: Tolerance of interferon is poor in haemodialysis patients. Sustained response is fairly high in patients who have 12 months of treatment and seems to be based on the immune status of the patients (ALT) and the cumulative doses of interferon.

Adult↗

PubMed2001

Improved survival in cancer patients requiring mechanical ventilatory support: impact of noninvasive mechanical ventilatory support.

OBJECTIVE: When a cancer patient becomes critically ill, mechanical ventilation (MV) is often considered futile. However, recent studies have found that outcomes of critically ill cancer patients have been improving over the years and that classic predictors of high mortality have lost their relevance. DESIGN: We retrospectively determined outcomes and predictors of 30-day mortality in 237 mechanically-ventilated cancer patients admitted to the intensive care unit (ICU). PATIENTS: The 132 (55.7%) patients who were admitted between 1990 and 1995 were compared with 105 (44.3%) patients who were admitted between 1996 and 1998. The malignancy was leukemia/lymphoma in 119 (50.3%) patients, myeloma in 50 (21%), and a solid tumor in 68 (28.7%). Forty-two (17.7%) patients had bone marrow transplantation, and 91 (38.4%) were neutropenic. Median Simplified Acute Physiology Score II (SAPS II) was 58 (range, 40-75). Reasons for MV were acute hypoxemic respiratory failure in 148 (62.5%) patients, coma in 54 (22.8%), and cardiogenic pulmonary edema in 35 (14.7%). Conventional MV was used first in 189 (79.8%) patients, and noninvasive MV (NIMV) was used in 48 (20.2%). Overall mortality rate was 72.5% (172 deaths). RESULTS: Logistic regression identified three variables associated with mortality: ICU admission between 1996 and 1998 (odds ratio [OR], 0.24; 95% confidence interval [CI], 0.12-0.50) and the use of NIMV (OR, 0.34; 95% CI, 0.16-0.73) were protective, and the SAPS II was aggravating (OR, 1.04 per point; 95% CI, 1.02-1.06). To better define the impact of NIMV, we performed a pairwise-matched exposed-unexposed analysis. Forty-eight patients who did and 48 who did not receive NIMV as the first ventilation method were matched for SAPS II, type of malignancy, and period of ICU admission. Crude ICU mortality rates from exposed patients and controls were 43.7% and 70.8%, respectively. NIMV remained protective from mortality after adjustment for matching variables (OR, 0.31; 95% CI, 0.12-0.82). CONCLUSION: Our results confirm that mortality has improved over the past decade in critically ill cancer patients, even those who require MV, and suggest that this may be, in part, because of a protective effect of NIMV.

APACHE↗

PubMed2001

French intensivists do not apply American recommendations regarding decisions to forgo life-sustaining therapy.

OBJECTIVE: Recommendations for making and implementing decisions to forgo life-sustaining therapy in intensive care units have been developed in the United States, but the extent that they are realized in practice has yet to be measured. DESIGN: Prospective, multicenter, 4-wk study. For each patient with an implemented decision to forgo life-sustaining therapy, the deliberation and decision implementation procedures were recorded. SETTING: French intensive care units. PATIENTS: All consecutive patients admitted to 26 French intensive care units. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1,009 patients admitted, 208 died in the intensive care unit. A decision to forgo life-sustaining therapy was implemented in 105 patients. The number of supportive treatments forgone was 2.3 +/- 1.7 per patient. Decisions to forgo sustaining therapy were preceded by 3.5 +/- 2.5 deliberation sessions. Proxies were informed of the deliberations in 62 (59.1%) cases but participated in only 18 (17.1%) decisions. The patient's perception of his or her quality of life was rarely evaluated (11.5%), and only rarely did the decision involve evaluating the patient's wishes (7.6%), the patient's religious values (7.6%), or the cost of treatment (7.6%). Factors most frequently evaluated were medical team advice (95.3%), predicted reversibility of acute disease (90.5%), underlying disease severity (83.9%), and the patient's quality of life as evaluated by caregivers (80.1%). CONCLUSIONS: A decision to withhold or withdraw life-sustaining therapy was implemented for half the patients who died in the French intensive care units studied. In many cases, the decision was taken without regard for one or more factors identified as relevant in U.S. guidelines.

Adult↗

PubMed2001

Symptoms of anxiety and depression in family members of intensive care unit patients: ethical hypothesis regarding decision-making capacity.

OBJECTIVE: Anxiety and depression may have a major impact on a person's ability to make decisions. Characterization of symptoms that reflect anxiety and depression in family members visiting intensive care patients should be of major relevance to the ethics of involving family members in decision-making, particularly about end-of-life issues. DESIGN: Prospective multicenter study. SETTING: Forty-three French intensive care units (37 adult and six pediatric); each unit included 15 patients admitted for longer than 2 days. PATIENTS: Six hundred thirty-seven patients and 920 family members. INTERVENTIONS: Intensive care unit characteristics and data on the patient and family members were collected. Family members completed the Hospital Anxiety and Depression Scale to allow evaluation of the prevalence and potential factors associated with symptoms of anxiety and depression. MEASUREMENTS AND MAIN RESULTS: Of 920 Hospital Anxiety and Depression Scale questionnaires that were completed by family members, all items were completed in 836 questionnaires, which formed the basis for this study. The prevalence of symptoms of anxiety and depression in family members was 69.1% and 35.4%, respectively. Symptoms of anxiety or depression were present in 72.7% of family members and 84% of spouses. Factors associated with symptoms of anxiety in a multivariate model included patient-related factors (absence of chronic disease), family-related factors (spouse, female gender, desire for professional psychological help, help being received by general practitioner), and caregiver-related factors (absence of regular physician and nurse meetings, absence of a room used only for meetings with family members). The multivariate model also identified three groups of factors associated with symptoms of depression: patient-related (age), family-related (spouse, female gender, not of French descent), and caregiver-related (no waiting room, perceived contradictions in the information provided by caregivers). CONCLUSIONS: More than two-thirds of family members visiting patients in the intensive care unit suffer from symptoms of anxiety or depression. Involvement of anxious or depressed family members in end-of-life decisions should be carefully discussed.

Anxiety↗

PubMed2001

Compliance with triage to intensive care recommendations.

DESIGN: Recommendations for triage to intensive care units (ICUs) have been issued but not evaluated. SETTING: In this prospective, multicenter study, all patients granted or refused admission to 26 ICUs affiliated with the French Society for Critical Care were included during a 1-month period. Characteristics of participating ICUs and patients, circumstances of triage, and description of the triage decision with particular attention to compliance with published recommendations were recorded. RESULTS: During the study period, 1,009 patients were and 283 were not admitted to the participating ICUs. Refused patients were more likely to be older than 65 yrs (odds ratio [OR], 3.53; confidence interval [CI], 1.98-5.32) and to have a poor chronic health status (OR, 3.09; CI, 2.05-4.67). An admission diagnosis of acute respiratory or renal failure, shock, or coma was associated with admission, whereas chronic severe respiratory and heart failure or metastatic disease without hope of remission were associated with refusal (OR, 2.24; CI, 1.38-3.64). Only four (range, 0-8) of the 20 recommendations for triage to ICU were observed; a full unit and triage over the phone were associated with significantly poorer compliance with recommendations (0 [0-2] vs. 6 [2-9], p =.0003; and 1 [0-6] vs. 6 [1-9], p <.0001; respectively). CONCLUSION: Recommendations for triage to intensive care are rarely observed, particularly when the unit is full or triage is done over the phone. These recommendations may need to be redesigned to improve their practicability under real-life conditions, with special attention to phone triage and triaging to a full unit.

Age Factors↗

PubMed2001

Induction of labour with a viable infant: a randomised clinical trial comparing intravaginal misoprostol and intravaginal dinoprostone.

OBJECTIVE: To compare the efficacy and safety of vaginal misoprostol (50 microg) with vaginal dinoprostone. DESIGN: Double-blind randomised trial. SETTING: Obstetrics Department, Poissy Hospital, France. PARTICIPANTS: 370 patients with medical indications for induction of labour. OUTCOME MEASURES: Vaginal deliveries within 24 hours, as well as time to vaginal deliveries, caesarean rates, costs, and fetal, neonatal and maternal condition. RESULTS: Compared with vaginal dinoprostone, vaginal misoprostol resulted in greater efficacy in several areas: vaginal delivery within 24 hours; time to vaginal delivery; and vaginal delivery within 12 hours. There was a non-significant increase in the caesarean section rate for fetal distress in the misoprostol group, but fewer caesarean sections for failed induction. Fetal tolerance was similar in the two groups, although significantly more neonates had a cord pH <7.20 and (non-significantly) none had meconium stained amniotic fluid in the misoprostol group. The incidence of poor neonatal outcome was similar in both groups. Subgroup analysis by indication for induction showed that the higher rates of arterial cord pH <7.20 and of meconium-stained amniotic fluid with misoprostol persisted only in possible fetal compromise. Poor neonatal outcome was less frequent in the misoprostol group in cases of induction for non-fetal indications. CONCLUSIONS: Vaginal misoprostol resulted in successful and earlier induction of labour more often than dinoprostone, but the safety of misoprostol raises some concern in potentially compromised infants. Misoprostol should be preferred to dinoprostone in cases of induction for non-fetal indications.

Administration, Intravaginal↗

PubMed2001

Intravenous immune globulins in patients with Guillain-Barré syndrome and contraindications to plasma exchange: 3 days versus 6 days.

Plasma exchange is contraindicated in 10 to 20% of patients with Guillain-Barré syndrome (GBS). The optimal schedule for intravenous immune globulin (IVIg) therapy has not yet been established in these patients. The objective was to compare the efficacy and safety of two IVIg treatment durations in patients with GBS with contraindications for plasma exchange. In this randomised, double blind, multicentre phase II trial conducted in seven French centres, patients with GBS with severe haemostasis, unstable haemodynamics, or uncontrolled sepsis were randomly assigned to 0.4 g/kg/day IVIg for 3 or 6 days. The primary outcome measure was the time needed to regain the ability to walk with assistance. Thirty nine patients were included from March 1994 to May 1997, 21 in the 3 day group and 18 in the 6 day group. Time to walking with assistance was non-significantly shorter in the 6 day group (84 (23-121) v 131 days (51-210), p=0.08); the difference was significant in ventilated patients (86 days (13-151) in the 6 day group v 152 days (54-332) in the 3 day group; p=0.04). The prevalence and severity of IVIg related adverse effects were comparable between the two groups. In conclusion, in patients with GBS and contraindications for plasma exchange, especially those who need ventilatory assistance, IVIg (0.4 g/kg/day) may be more beneficial when given for 6 days rather than 3 days.

Aged↗

PubMed2001

Meeting the needs of intensive care unit patient families: a multicenter study.

Intensive care unit (ICU) caregivers should seek to develop collaborative relationships with their patients' family members, based on an open exchange of information and aimed at helping family members cope with their distress and allowing them to speak for the patient if necessary. We conducted a prospective multicenter study of family member satisfaction evaluated using the Critical Care Family Needs Inventory. Forty-three French ICUs participated in the study. ICU characteristics, patient and family member demographics, and data on satisfaction were collected. Factors associated with satisfaction were identified using a Poisson regression model. A total of 637 patients were included in the study, and 920 family members completed the questionnaire. Seven predictors of family satisfaction were found: one family-related factor, namely, family of French descent and six caregiver-related factors, namely, no perceived contradictions in information given by caregivers; information provided by a junior physician; patient to nurse ratio </= 3; knowledge of the specific role of each caregiver; help from the family's own doctor; and sufficient time spent giving information. Predictors of satisfaction are amenable to intervention and deserve to be investigated further with the goal of improving the satisfaction of ICU patients' family members.

Adult↗

PubMed2000

Infection as a trigger of diabetic ketoacidosis in intensive care-unit patients.

We determined the prevalence and indicators of infection in intensive care unit (ICU) patients with diabetic ketoacidosis (DKA) by performing a retrospective analysis of 123 episodes of DKA (in 113 patients) managed in a medical ICU between 1990 and 1997. In univariate analysis, features associated with infection were female sex, neurological symptoms at admission, fever during the week before admission, a need for colloids, a high blood lactate level at admission, and lack of complete clearance of ketonuria within 12 h. Multivariate analysis identified 3 independent predictors of infection: female sex (odds ratio [OR], 2.31; confidence interval [CI], 1.05-5.35), neurological symptoms at admission (OR, 2.83; CI, 1.18-6.8), and lack of complete clearance of ketonuria within 12 h (OR, 3.73; CI, 1.58-9.09). Infection is the leading trigger of DKA in ICU patients. Neurological symptoms at admission and lack of complete clearance of ketonuria within 12 h are useful warning signals of infection.

Adult↗

PubMed2000

Rapid diagnosis of infectious pleural effusions by use of reagent strips.

Reagent strips have not yet been tested for use in the diagnosis of infectious pleural effusions. A reagent strip was used to evaluate 82 patients with pleural effusions: 20 patients had transudative effusions, 35 had infectious exudative effusions (empyema in 14 and parapneumonic effusion in 21), and 27 had noninfectious exudative effusions. Pleural fluid protein, as evaluated by the reagent strip, proved accurate for the detection of exudative effusions (sensitivity, 93.1%; specificity, 50%; positive predictive value, 84.3%; negative predictive value, 71.5%; odds ratio [OR], 6.77; and 95% confidence interval [CI], 1.87-24). The reagent strip leukocyte esterase test effectively detected infectious exudative effusions (sensitivity, 42.8%; specificity, 91.3%; positive predictive value, 88.2%; negative predictive value, 51.2%; OR, 4.46; and 95% CI, 1.2-16.4). Pleural pH was significantly predicted by the reagent strip but was of no assistance in categorization of exudative effusions as infectious or noninfectious. Compared with physical, laboratory, and microbiological data, the reagent strip was as accurate for estimation of percentages of infectious and noninfectious exudative effusions. Thus, reagent strips may be a rapid, easy-to-use, and inexpensive technique for discriminating transudative from exudative pleural effusions and for categorizing exudative pleural effusions as infectious or noninfectious.

Adult↗

PubMed2000

Constitutive elevation of serum alpha-fetoprotein in Fanconi anemia.

The diagnosis of Fanconi anemia (FA) is based on the association of congenital malformations, bone marrow failure syndrome, and hypersensitivity to chromosomal breaks induced by cross-linking agents. In the absence of typical features, the diagnosis is not easy to establish because there is no simple and cost-effective test; thus, investigators must rely on specialized analyses of chromosomal breaks. Because we observed elevated serum alpha-fetoprotein (sAFP) levels in FA patients, we investigated this parameter as a possible diagnostic tool. Serum AFP levels from 61 FA patients and 27 controls with acquired aplastic anemia or other inherited bone marrow failure syndromes were analyzed using a fluoroimmunoassay based on the TRACE technology. Serum AFP levels were significantly more elevated (P <.0001) in FA than in non-FA aplastic patients. In the detection of FA patients among patients with bone marrow failure syndromes, this assay had a sensitivity of 93% and a specificity of 100%. This elevation was not explained by liver abnormalities. Levels of sAFP were unchanged during at least 4 years of follow-up, and allogeneic bone marrow transplantation did not modify sAFP levels. Three of 4 FA patients with mosaicism as well as 5 of 6 FA patients with myelodysplastic syndrome were detected by this test. Heterozygous parents of FA patients had normal sAFP levels. Measurement of sAFP levels with this automated, cost-effective, and reproducible fluoroimmunoassay could be proposed for the preliminary diagnosis of FA whenever this disorder is suspected.

Adolescent↗

PubMed2000

Measures of treatment effectiveness on tumour response and survival: a multi-state model approach.

This paper proposes the application of a counting process approach in the analysis of treatment effect on tumour response and survival. It relies on the definition of two transient states between which individuals may move over time, that is, response and non-response, and of one absorbing state, death. Three models are discussed according to the underlying Markov and duration dependence assumptions, as well as a marginal modelling of repeated transitions between the two transient states. We illustrate the proposed methods with data from a randomized clinical trial assessing the effect of fludarabine in patients with advanced chronic lymphocytic leukaemia.

Antineoplastic Agents↗

PubMed2000

Nocturnal mechanical ventilation for chronic hypoventilation in patients with neuromuscular and chest wall disorders.

BACKGROUND: Chronic alveolar hypoventilation is a common complication of many neuromuscular and chest wall disorders. Long term nocturnal mechanical ventilation is used to treat an increasing number of patients. OBJECTIVES: To examine the efficacy of nocturnal mechanical ventilation in relieving hypoventilation related symptoms in patients with neuromuscular or chest wall disorders. SEARCH STRATEGY: Search of the Cochrane Neuromuscular Disease Group register for randomized trials and enquiry from authors of trials and other experts in the field. SELECTION CRITERIA: Types of studies: quasi-randomized or randomized controlled trials TYPES OF PARTICIPANTS: patients with neuromuscular or chest wall disorder-related stable chronic hypoventilation of all ages and all degrees of severity. Types of interventions: any type and any mode of nocturnal mechanical ventilation. Types of outcome measures: Primary: short term and long term reversal of hypoventilation related clinical symptoms Secondary: unplanned hospital admission rate, one year mortality, short term and long term reversal of day time hypercapnia, improvement of lung function and improvement of sleep breathing disorders. DATA COLLECTION AND ANALYSIS: We identified four randomized trials. One author extracted the data and another checked them. Individual data were available from the authors of the largest study. MAIN RESULTS: The four eligible trials included a total of 51 patients. The risk difference (proportion of patients) of no improvement of hypoventilation related clinical symptoms in the short term following nocturnal mechanical ventilation was significant and favoured treatment, -0.417 (95% CI -0.639 to -0.194). However, there was significant heterogeneity across the studies (p<0.001). Similarly, the risk difference of no reversal of day time hypercapnia in the short term following nocturnal ventilation was significant and favoured treatment, -0.635 (95% CI -0.874 to -0.396). The weighted mean difference of nocturnal mean oxygen saturation percent was 5.5 (95% CI 1.5 to 9.4) more improvement in patients treated with nocturnal mechanical ventilation. For the primary and most of the secondary outcome measures there was no significant difference between nocturnal mechanical ventilation and no ventilation in the long term, except for one-year mortality. Indeed, the risk difference of death one year following implementation of nocturnal mechanical ventilation was significant and favoured treatment, -0.259 (95% CI -0.478 to -0. 041). However, there was significant heterogeneity across the studies (p<0.001). Most of the secondary outcomes were not assessed in the eligible trials. No data could be summarised for the comparisons between invasive and non-invasive mechanical ventilation, between intermittent positive pressure and negative pressure ventilation, and between volume-cycled and pressure-cycled ventilation. REVIEWER'S CONCLUSIONS: Current evidence about the therapeutic benefit of mechanical ventilation is weak, but consistent, suggesting alleviation of the symptoms of chronic hypoventilation in the short term, and in two small studies survival was prolonged. Mechanical ventilation should be offered as a therapeutic option to patients with chronic hypoventilation due to neuromuscular diseases. Further larger randomized trials are needed to confirm long term beneficial effects of nocturnal mechanical ventilation on quality of life, morbidity and mortality, to assess its cost-benefit ratio, and to compare the different types and modes of ventilation.

Chronic Disease↗

PubMed2000

Validity and reliability of two muscle strength scores commonly used as endpoints in assessing treatment of myasthenia gravis.

Valid and reliable measurements of muscle impairment are needed to assess therapeutic efficacy in patients with generalized myasthenia gravis (MG). In 22 patients we compared the validity and interobserver reliability of two scoring methods commonly used as main endpoints in clinical trials, i.e., the Myasthenic Muscle Score (MMS) ranging from 0 to 100 (normal) and the Quantified Myasthenia Gravis Strength Score (QMGSS) ranging from 0 (normal) to 39. Each score is correlated more with functional scale and less with the patient's self-evaluation. Using intraclass correlation we found strong agreement between observers for both the MMS (r = 0.906) and the QMGSS (r = 0.905). The correlation between MMS and QGMSS was high (r = 0.87). The reliability of neither score depended on any specific item, since the removal of individual items did not significantly alter the intraclass correlation coefficient (ranging from 0.86 to 0.93).

Adult↗