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Biomedical subjects

D Annane

Publications and source records attributed to D Annane.

At least 19 recordsLinked to original sources
PubMed2006

Psychostimulants for hypersomnia (excessive daytime sleepiness) in myotonic dystrophy.

BACKGROUND: Excessive daytime sleepiness is a common symptom of myotonic dystrophy. Psychostimulants are drugs increasingly used to treat hypersomnia in myotonic dystrophy. OBJECTIVES: To search systematically for, and combine all evidence from, randomised trials relating to the effects of psychostimulants in myotonic dystrophy patients with hypersomnia. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Trials Register (January 2006), MEDLINE (from January 1966 to January 2006) and EMBASE (from January 1980 to January 2006) for randomised trials concerning psychostimulants in myotonic dystrophy, checked the bibliographies of identified papers and made enquiries of the authors of the papers. The search for relevant studies was updated in January 2006. SELECTION CRITERIA: We considered all randomised or quasi randomised trials that have evaluated any type of psychostimulants (versus a placebo or no treatment) in children or adults with proven myotonic dystrophy and hypersomnia. DATA COLLECTION AND ANALYSIS: Potentially relevant papers were scrutinised by two authors and the selection of eligible studies was agreed by them and a third author. Data were extracted by one author and checked by a second author. MAIN RESULTS: Primary outcome. One trial using a modified maintenance of wakefulness test showed an improvement by 5.70 (95% confidence intervals 0.1 to 11.3) minutes more in the modafinil than the control group. Secondary outcomes. In a double-blind crossover study of 10 participants with myotonic dystrophy, there was no difference between the selegiline and placebo periods in mean improvement in the multiple sleep latency test. Two trials, involving 60 participants in total, evaluated the efficacy and safety of modafinil in adults with myotonic dystrophy-related daytime sleepiness. The weighted mean difference on the Epworth Sleepiness Scale was -1.59 (95% confidence intervals, -2.77 to -0.42) in favour of modafinil. AUTHORS' CONCLUSIONS: There is no evidence to support the routine use of psychostimulants to treat hypersomnia in myotonic dystrophy. There is some evidence from two studies that modafinil may improve daytime sleepiness. More randomised trials are needed to evaluate the efficacy and safety of psychostimulants.

Benzhydryl Compounds↗
PubMed2006

Glucocorticoid treatment in patients with septic shock: effects on vasopressor use and mortality.

Corticosteroids were proposed for the treatment of sepsis as early as 1940. Several RCTs cast serious doubts on the usefulness of high dose corticosteroids and doubt still persists regarding the efficacy of replacement therapy. Adrenal insufficiency (non-responders to the 250 microg corticotropin test: increase in cortisol < 9 microg/dl) is present in about half of patients with septic shock and is associated with higher rates of refractory hypotension and mortality. Peripheral glucocorticoid resistance, which may even occur more frequently, can be easily assessed at bedside using skin tests. Cortisol antagonizes the migration of inflammatory cells, the synthesis or action of virtually all proinflammatory mediators, promotes virtually all anti-inflammatory components and enhances humoral immunity by means of transcriptional interference between its receptor and both AP-1 and NF-kappaB. Cortisol mediates cardiovascular tolerance to endotoxin and the maintenance of vascular sensitivity to catecholamines. Low doses (about 300 mg daily for 5 days or more) of hydrocortisone increase vasoconstrictor response to catecholamines in animals, in healthy volunteers challenged with LPS and in several RCTs. Hydrocortisone also increases arterial pressure and decreases the duration of shock. A meta-analysis of all available clinical controlled studies showed a reduction in 28 days, all-cause mortality with glucocorticoids (RR = 0.88, 95% CI: 0.78 - 1.00; p = 0.04). However, there was a significant heterogeneity across the trials (p = 0.006). On the other hand, analysis of studies where low doses of glucocorticoids were given for prolonged periods showed a 24% reduction in the risk of all-cause mortality at 28 days in treated patients (RR = 0.76, 95% CI: 0.64 - 0.90; p = 0.002) without heterogeneity across the trials (p = 0.28). In conclusion, in severe sepsis, high doses of corticosteroids should not be given. Septic shock should be treated with a replacement dose of hydrocortisone.

Apoptosis↗
PubMed2005

Glucocorticoids and sepsis.

Although systemic inflammation is the hallmark of sepsis, the use of glucocorticoids remained controversial during many years. Gluco-corticoids exert key actions during sepsis, interacting with metabolism, immune and cardiovascular systems. Glucocorticoid insufficiency is common during sepsis and may result from insufficient production of cortisol or peripheral tissues resistance. Thus, recent randomised trials showed that a replacement therapy with long course of low dose corticosteroids reduced mortality from septic shock. Improvement in survival may result from reduced duration of shock, alleviation of the systemic inflammatory response, and reduction in the number and intensity of organs dysfunction. This article summarises why, when and how glucocorticoids should be used in the management of septic shock.

Anti-Inflammatory Agents↗
PubMed2004

Corticosteroids for treating severe sepsis and septic shock.

BACKGROUND: Sepsis may be complicated by impaired corticosteroid production. Giving corticosteroids could potentially benefit patients. OBJECTIVES: To examine the effects of corticosteroids on death at one month in patients with severe sepsis and septic shock. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group's trial register (August 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2003), MEDLINE (August 2003), EMBASE (August 2003), LILACS (August 2003), reference lists of articles, and also contacted trial authors. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials of corticosteroids versus placebo or supportive treatment in severe sepsis and septic shock. DATA COLLECTION AND ANALYSIS: Two pairs of reviewers agreed the eligibility of trials. One reviewer extracted data, which was checked by the other reviewers and the primary author of the paper whenever possible. We obtained some missing data from the trial authors. We assessed trial methodological quality. MAIN RESULTS: We identified 15 trials (n =2023). Corticosteroids did not change 28-day all-cause mortality (15 trials, n = 2022, relative risk (RR) 0.92, 95% confidence interval (CI) 0.75 to 1.14; random effects model) and hospital mortality (13 trials, n = 1418, RR 0.89, 95% CI 0.71 to 1.11; random effects model); however, there was statistically significant heterogeneity, with some evidence that this was related to the dosing strategy. Corticosteroids reduced intensive care unit mortality (4 trials, n = 425, RR 0.83, 95% CI 0.70 to 0.97), increased the proportion of shock reversal by day 7 (6 trials, n = 728, RR 1.22, 95% CI 1.06 to 1.40) and by day 28 (4 trials, n = 425, RR 1.26, 95% CI 1.04 to 1.52), without increasing the rate of gastroduodenal bleeding (10 trials, n = 1321, RR 1.16, 95% CI 0.82 to 1.65), superinfection (12 trials, n = 1705, RR 0.93, 95% CI 0.73 to 1.18), and of hyperglycaemia (6 trials, n = 608, RR 1.22, 0.84 to 1.78). REVIEWER'S CONCLUSIONS: Overall, corticosteroids did not change 28-day mortality and hospital mortality in severe sepsis and septic shock. Long course of low dose corticosteroids reduced 28-day all-cause mortality, and intensive care unit and hospital mortality.

Adrenal Cortex Hormones↗
PubMed2003

Sepsis clinical knowledge: a role of steroid treatment.

After a period of initial enthusiasm, several trials cast serious doubts on the usefulness of corticosteroids for the treatment of patients with severe sepsis. Short course with high doses of steroides should not be given in patients with severe sepsis. The attention is now addressed to low-dose of corticosteroides. The rational for a replacement therapy with hydrocortisone in patients with cathecolamines-dependent septic shock is based on the concept that this may be complicated by an occult adrenal insufficiency and a glucocorticoid peripheral resistance syndrome. Low doses of hydrocortisone has been shown to reproduce the normal effects of cortisol: anti-inflammatory properties and an increased in the vasoconstrictor response to cathecolamines. There is no concordance in literature about the role of replacement therapy with hydrocortisone on survival in patients with septic shock. Waiting for the results of the European confirmatory phase III trial, and based on the results of the French phase III trial, one may recommended to treat septic shock patients who have a cortisol increment after ACTH of less than 9 micro g/dl with 50 mg of hydrocortisone every 6 hours for seven days combined with 50 micro g of fludrocortisone once a day for seven days.

Anti-Inflammatory Agents↗
PubMed2002

Psychostimulants for hypersomnia (excessive daytime sleepiness) in myotonic dystrophy.

BACKGROUND: Excessive daytime sleepiness is a common symptom of myotonic dystrophy. Psychostimulants are drugs increasingly used to treat hypersomnia in myotonic dystrophy. OBJECTIVES: To search systematically for, and combine all evidence from, randomised trials relating to the effects of psychostimulants in myotonic dystrophy patients with hypersomnia. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Trial Register (searched May 2001) for randomised trials concerning psychostimulants in myotonic dystrophy, we searched of the bibliographies of identified papers and we contacted the authors of the papers. SELECTION CRITERIA: We considered all randomised or quasi randomised trials that have evaluated any type of psychostimulants (versus a placebo or no treatment) in children or adults with proven myotonic dystrophy and hypersomnia. DATA COLLECTION AND ANALYSIS: Potentially relevant papers were scrutinised by two reviewers and the selection of eligible studies was agreed by them and a third reviewer. Data were extracted by one reviewer and checked by a second reviewer. MAIN RESULTS: Primary outcome We found no trial that assessed the effect of a psychostimulant on the results of the maintenance of wakefulness tests. Secondary outcomes Only one eligible trial was found. In this crossover double blind study of 10 patients with myotonic dystrophy, the efficacy of selegiline was evaluated against a placebo on the multiple sleep latency test. There was no difference between the selegiline and placebo periods in mean improvement in the multiple sleep latency test scale. REVIEWER'S CONCLUSIONS: There is no evidence to support the use of a psychostimulant to treat hypersomnia in myotonic dystrophy. Randomised trials are needed to evaluate the efficacy and safety of psychostimulants.

Disorders of Excessive Somnolence↗
PubMed2002

Resurrection of steroids for sepsis resuscitation.

Corticosteroids were proposed to treat patients with severe sepsis as early as 1940. A summary of all available randomized controlled trials performed between 1966 and 1993 was provided in two systematic review that recommended to abandon the use of high dose coricosteroids to treat patients with severe infection. Nonetheless, a doubt still persist regarding the efficacy of a strategy of replacement therapy in cathecolamines-dependent shock. This strategy relies mainly on the concept that septic shock may be complicated by 1) an occult adrenal insufficiency, 2) a glucocorticoid peripheral resistance syndrome. Some studies demonstrated the effect of replacement therapy with hydrocortisone on the sistemic inflammatory response and on the cardiovascular function during sepsis. The effect of this therapy on survival to septic shock is controversial both in recent and old studies. Finally a recently completed multicenter, placebo controlled, randomized, double-blind study has evaluated the efficacy and tolerance of a replacement therapy with a combination of hydrocortisone (50 mg intravenous bolus four times per day) and fludrocortisone (50 g orally once a day) given for 7 days. This study included 300 catecholamines- and ventilator-dependent septic shock. The authors found a significant reduction in 28-day mortality in patient with occult renal insufficiency. In sum, short course with high doses of corticosteroids should not be given in severe sepsis, except for specific entitles like severe typhoid fever, pneumocystis carinii pneumonia in AIDS or bacterial meningitis in children. The rational for a replacement therapy with hydrocortisone in catecholamines-dependent septic shock grows stronger.

Adrenal Cortex↗
PubMed2001

Prognostic factors in unintentional mild carbon monoxide poisoning.

OBJECTIVES: To identify early predictors of recovery from mild carbon monoxide poisoning, and to search for qualitative interactions between subsets of patients and treatment effects. DESIGN AND SETTING: Inception cohort study from a 4-year, randomised, controlled trial, which compared normobaric oxygen therapy to the combination of normobaric plus hyperbaric oxygen therapy in 307 patients. Study was conducted at a hyperbaric oxygen therapy referral centre. PATIENTS AND INTERVENTIONS: Victims of unintentional, non-fire-related, domestic, carbon monoxide intoxication were evaluated if the time elapsed from end of exposure to hospital admission was less than 12 h, the carboxyhaemoglobin level was greater than or equal to 10% or 5% for smoker or non-smoker, respectively, and if they did not suffer a loss of consciousness. One course of hyperbaric oxygen therapy or 6-h normobaric oxygen therapy was given. MEASUREMENTS AND RESULTS: The main outcome measure was status at the 1-month recovery. Of the 307 evaluated patients, 206 (67%, 95%CI: 62%-72%) had recovered at 1 month. None of the patients died or suffered severe sequelae. Apathy and headaches were the main moderate sequelae. The multivariate analysis selected dizziness before admission (OR=1.92, [1.17-3.15], p=0.010) and headaches upon hospital admission (OR=2.14, [1.09-4.17], p=0.026) as jointly associated with persistent neurological symptoms. No significant crossover interaction between each combination of these two predictors and treatment effects was observed. CONCLUSIONS: At 1 month after mild carbon monoxide intoxication, victims who presented with dizziness before hospital admission or headaches upon admission have an increased risk of minor persistent neurological symptoms, but almost all patients could resume their former occupation.

Adult↗
PubMed2001

Plasma exchange for Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome is an acute symmetric usually ascending and usually paralysing illness due to inflammation of peripheral nerves. It is thought to be caused by autoimmune factors, such as antibodies. Plasma exchange removes antibodies and other potentially injurious factors from the blood stream. It involves connecting the patient's blood circulation to a machine which exchanges the plasma for a substitute solution, usually albumin. Several studies have evaluated plasma exchange for Guillain-Barré syndrome. OBJECTIVES: To systematically review the evidence concerning the efficacy of plasma exchange for treating Guillain-Barré syndrome. SEARCH STRATEGY: Search of the Cochrane Neuromuscular Disease Trial Register for randomised trials concerning plasma exchange in Guillain-Barré syndrome, search of the bibliographies of identified papers and enquiry from the authors of the papers. SELECTION CRITERIA: Randomised and quasi-randomised trials of plasma exchange versus sham exchange or supportive treatment. DATA COLLECTION AND ANALYSIS: Potentially relevant papers were scrutinised by two reviewers and the selection of eligible studies was agreed by them and a third reviewer. Data were extracted by one reviewer and checked by a second reviewer. Some missing data were obtained from the authors of studies. MAIN RESULTS: Six eligible trials concerning 649 patients were identified, all comparing plasma exchange versus supportive treatment alone. Primary outcome measures ~Bullet~Time to recover walking with aid In the only two trials for which this measure was reported the median time to recover this ability was faster in the plasma exchange than the control group. ~Bullet~Time to onset of motor recovery in mildly affected patients In the one trial for which this measure was available the time was significantly shortened in the plasma exchange group. Secondary outcome measures ~Bullet~Improvement in disability grade at 4 weeks In five trials, there were significantly more patients who had improved by one disability grade or more in the plasma exchange group as compared to the control group. Patients treated with plasma exchange fared significantly better in the following secondary outcome measures: time to recover walking without aid, percentage of patients requiring artificial ventilation, duration of ventilation, full muscle strength recovery after one year, and severe sequelae after one year. There were less patients with infectious events and cardiac arrhythmias in the plasma exchange than the control group. Subgroup analyses Plasma exchange was beneficial in patients with mild, moderate and severe (needing ventilation) Guillain-Barré syndrome. It was beneficial in patients with a disease duration of seven or less days and also in those with disease lasting more than seven days. However, in the only trial that enrolled patients up to 30 days from disease onset, the benefit of plasma exchange in patients treated after seven days was less apparent. Type of treatment Single studies showed that two plasma exchanges were significantly superior to none for mild Guillain-Barré syndrome and four to two for moderate Guillain-Barré syndrome but that six were not superior to four for severe Guillain-Barré syndrome requiring ventilation. One study suggested that continuous flow plasma exchange was significantly superior to intermittent flow. Another study found no significant difference between the two techniques. The same study found a significantly higher rate of adverse events with fresh frozen plasma as the replacement fluid than albumin. REVIEWER'S CONCLUSIONS: Plasma exchange is the first and only treatment that has been proven to be superior to supportive treatment alone in Guillain-Barré syndrome. Consequently, plasma exchange should be regarded as the treatment against which new treatments, such as intravenous immunoglobulin, should be judged. In mild Guillain-Barré syndrome two sessions of plasma exchange are superior to none. In moderate Guillain-Barré syndrome four sessions are superior to two. In severe Guillain-Barré syndrome six sessions are no better than four. Continuous flow plasma exchange machines may be superior to intermittent flow machines and albumin to fresh frozen plasma as the exchange fluid. Plasma exchange is more beneficial when started within seven days after disease onset rather than later, but was still beneficial in patients treated up to 30 days after disease onset. The value of plasma exchange in children less than 12 years old is not known.

Guillain-Barre Syndrome↗
PubMed2001

Supine fall in lung volumes in the assessment of diaphragmatic weakness in neuromuscular disorders.

OBJECTIVE: To determine whether diaphragmatic function can be determined by noninvasive respiratory indices in neuromuscular disease. DESIGN: Vital capacity (VC) and mouth pressure generated during a maximal static inspiratory effort (Pi max) were measured with patients in both sitting and supine positions. SETTING: Rehabilitation hospital. PATIENTS: Twenty-four patients with generalized neuromuscular disease. MAIN OUTCOME MEASURES: Changes in indices from sitting to supine position were compared with invasive diaphragmatic function indices consisting of transdiaphragmatic pressures during maximal sniff (Pdi sniff) and the ratio of gastric pressure (Pga) increases over transdiaphragmatic pressure (DeltaPga/DeltaPdi) during quiet breathing. RESULTS: The fall in VC in the supine position was greater in the 15 patients who had spontaneous paradoxical diaphragmatic motion (DeltaPga/DeltaPdi < 0) than in the 9 patients who did not. Specificity and sensitivity of a greater than 25% supine fall in VC for the diagnosis of diaphragmatic weakness (DeltaPga/DeltaPdi < 0 and/or Pdi sniff < 30cmH2O) were 90% and 79%, respectively. Stepwise multiple regression analysis of Pdi sniff showed that both the supine fall in VC and Pi max were associated with diaphragmatic weakness (R(2) =.66; p <.0001). These factors contributed 52% and 14% of the Pdi sniff variance, respectively. CONCLUSIONS: Simple VC measurement in the sitting and supine positions may be helpful in detecting severe or predominant diaphragmatic weakness.

Adult↗
PubMed2001

Cardiac variability in critically ill adults: influence of sepsis.

OBJECTIVE: To evaluate, in critically ill adults, factors associated with impaired sympathovagal balance. DESIGN: One-month inception cohort study. SETTING: Twenty-six-bed medical intensive care unit of a teaching hospital. PATIENTS: Critically ill adults with an expected duration of intensive care unit stay of > or =48 hrs were enrolled. Patients with permanent arrhythmia or cardiac pacing were not included. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Sympathovagal balance was assessed on the day after intensive care unit admission by the low-frequency/high-frequency ratio obtained from spectral components of heart rate signal: overall variability, low frequency, and high frequency. RESULTS: Forty-one patients, 13 with sepsis and 28 without sepsis, were assessed. Predictors of low-frequency/high-frequency ratio with the automatic interaction detection method were sepsis and age. Binary logit analysis adjusted for age showed that sepsis remained a strong and independent factor of a low-frequency/high-frequency ratio of <1.50, with an odds ratio of 3.63 (95% confidence interval, 1.47-9.01, p =.005). Use of mechanical ventilation, catecholamines, or sedation did not add any information. The use of the low-frequency/high-frequency ratio in diagnosing sepsis may be supported by a likelihood ratio for low frequency/high frequency <1 at 6.47. CONCLUSIONS: This work suggests that impaired cardiac variability and notably sympathovagal balance (i.e., a low-frequency/high-frequency ratio <1.0) may be a diagnostic test for sepsis.

Adult↗
PubMed2001

Corticosteroids for septic shock.

OBJECTIVE: To gather the data to provide a rationale for using replacement therapy with hydrocortisone in septic shock patients. DATA SOURCES: The Medline and the Cochrane Library databases. STUDY SELECTION: Studies in animals and in humans were considered when significant data were available about the mechanisms of action of corticosteroids or about their use in severe sepsis. DATA SUMMARY: Corticosteroids were the first anti-inflammatory drugs tested in septic patients. Randomized trials clearly showed that a short course of a large dose of anti-inflammatory steroids is ineffective and potentially harmful in patients with severe sepsis. Recent demonstrations of altered hypothalamic-pituitary-adrenal axis response to septic insult have led to a reappraisal of the use of steroids in septic shock. Randomized trials in catecholamine-dependent septic shock patients strongly suggest that replacement therapy with hydrocortisone may alleviate the symptoms of systemic inflammatory response, reduce the duration of shock, and favorably affect survival. CONCLUSIONS: Current evidence that the therapeutic interest of replacement therapy with corticosteroids increases suggests that low doses of hydrocortisone should be offered to patients with catecholamine-dependent septic shock.

Adrenal Insufficiency↗
PubMed2001

Replacement therapy with hydrocortisone in catecholamine-dependent septic shock.

Septic shock is one of the leading causes of death in intensive care units world-wide. Scientists have made great improvements in understanding mechanisms of inflammation, and the sequence of activation of the various pro- and anti-inflammatory markers is now well known. In contrast, physicians have failed to improve survival from septic shock despite the development of specific targets at various points in the cytokine cascade considered to have a key role in host survival in sepsis. Corticosteroids were among the first anti-inflammatory drugs to be tested in large randomized controlled trials. These trials showed that patients with septic shock did not benefit from a short course of large doses of steroids. More recent findings highlighting the role of the integrity of the hypothalamic-pituitary-adrenal axis to respond appropriately to a septic insult, have led to a re-appraisal of the use of steroids in septic shock. Several randomized controlled trials have evaluated the efficacy of a replacement therapy with hydrocortisone in severe sepsis. These trials strongly suggest that this replacement therapy reduces the morbidity of septic shock and may favorably affect survival from septic shock.

Animals↗
PubMed2000

Compartmentalised inducible nitric-oxide synthase activity in septic shock.

BACKGROUND: Previous experimental studies support a role for inducible nitric-oxide synthase (iNOS) in the pathogenesis of severe sepsis. The aim of the study was to characterise iNOS activity in different tissues in patients with septic shock. METHODS: 13 consecutive patients with septic shock caused by cellulitis were enrolled. Skin, muscle, fat, and artery samples were obtained from normal, inflamed, and putrescent areas to measure iNOS activity, and concentrations of tumour necrosis factor alpha (TNFalpha) and interleukin 1beta (IL-1beta). In two patients, iNOS activity was also assessed in peripheral blood mononuclear cells (PBMC) incubated with microorganisms causing the sepsis, or in macrophages isolated from suppurating peritoneal fluid incubated with IL-1beta. FINDINGS: Compared with normal and inflamed areas, iNOS activity was increased in putrescent areas for muscle (71-fold [95% CI 20-259] vs normal areas, 69-fold [19-246] vs inflamed areas; p<0.01 for each) and for fat (68-fold [23-199] and 49-fold [18-137], respectively; p<0.01), but not for skin. Compared with normal areas, putrescent areas of arteries showed increased iNOS expression (1280-fold [598-3153]; p<0.01). Compared with normal areas, TNFalpha and IL-1beta were increased in putrescent areas of arteries (223-fold and 41-fold, respectively; p<0.01 for each). PBMCs and tissue macrophages expressed iNOS. Plasma nitrite/nitrate concentrations inversely correlated with mean arterial pressure and systemic vascular resistance. INTERPRETATION: In human septic shock we found that iNOS activity is compartmentalised at the very site of infection and parallels expression of TNFalpha and IL-1beta. PBMCs and tissue macrophages can be a cellular source for iNOS.

Adipose Tissue↗