Disagreement Between Clinicians and Score in Decision-Making Capacity of Critically Ill Patients.

OBJECTIVES: To compare the assessment of decision-making capacity of ICU patients by attending clinicians (physicians, nurses, and residents) with a capacity score measured by the Mini-Mental Status Examination, completed by Aid to Capacity Evaluation if necessary. The primary outcome was agreement between physicians' assessments and the score. Secondary outcomes were agreement between nurses' or residents' assessments and the score and identification of factors associated with disagreement. DESIGN: A 1-day prevalence study. SETTING: Nineteen ICUs in France. SUBJECTS: All patients hospitalized in the ICU on the study day and the attending clinicians. INTERVENTIONS: The decision-making capacity of patients was assessed by the attending clinicians and independently by an observer using the score. MEASUREMENTS AND MAIN RESULTS: A total of 206 patients were assessed by 213 attending clinicians (57 physicians, 97 nurses, and 59 residents). Physicians designated more patients as having decision-making capacity (n = 92/206 [45%]) than score (n = 34/206 [17%]; absolute difference 28% [95% CI, 20-37%]; p = 0.001). There was a high disagreement between assessments of all clinicians and score (Kappa coefficient 0.39 [95% CI, 0.29-0.50] for physicians; 0.39 [95% CI, 0.27-0.52] for nurses; and 0.46 [95% CI, 0.35-0.58] for residents). The main factor associated with disagreement was a Glasgow Coma Scale score between 10 and 15 (odds ratio, 2.92 [1.18-7.19], p = 0.02 for physicians; 4.97 [1.50-16.45], p = 0.01 for nurses; and 3.39 [1.12-10.29], p = 0.03 for residents) without differentiating between the Glasgow Coma Scale scores from 10 to 15. CONCLUSIONS: The decision-making capacity of ICU patients was largely overestimated by all attending clinicians as compared with a score. The main factor associated with disagreement was a Glasgow Coma Scale score between 10 and 15, suggesting that clinicians confused consciousness with decision-making capacity.

Electrolytes-Enriched Hemodiafiltration Solutions for Continuous Renal Replacement Therapy in Acute Kidney Injury: A Crossover Study.

AIMS: To evaluate the capability of an electrolytes-enriched solution to prevent metabolic disorders during continuous veno-venous hemodiafiltration (CVVHDF). METHODS: Serum biochemistry and clinical tolerance were compared during CVVHDF treatments with an electrolyte-enriched (Phoxilium) or standard solutions in 10 acute renal failure patients. RESULTS: As compared to standard fluids, serum potassium and phosphate levels were maintained in the normal range with Phoxilium without any supplementation but total serum calcium levels were significantly lower. Bicarbonatemia was slightly higher (24-26 vs. 21.5-24.5 mmol/l, p < 0.05) with conventional solutions and was associated with a significant increased level of pH (>7.44). Despite the absence of glucose in the Phoxilium solution, blood glucose levels and glucose supplementation were similar between treatments. Clinical tolerance and efficiency of CVVHDF sessions were comparable. CONCLUSION: Phoxilium effectively prevented hypophosphatemia and hypokalemia during CVVHDF. It was, however, associated with a slight metabolic acidosis and hypocalcemia compared with conventional solutions.

Comparison of two methods to report potentially avoidable hospitalizations in France in 2012: a cross-sectional study.

BACKGROUND: Potentially avoidable hospitalizations represent an indirect measure of access to effective primary care. However many approaches have been proposed to measure them and results may differ considerably. This work aimed at examining the agreement between the Weissman and Ansari approaches in order to measure potentially avoidable hospitalizations in France. METHODS: Based on the 2012 French national hospital discharge database (Programme de Médicalisation des Systèmes d'Information), potentially avoidable hospitalizations were measured using two approaches proposed by Weissman et al. and by Ansari et al. Age- and sex-standardised rates were calculated in each department. The two approaches were compared for diagnosis groups, type of stay, severity, age, sex, and length of stay. RESULTS: The number and age-standardised rate of potentially avoidable hospitalizations estimated by the Weissman et al. and Ansari et al. approaches were 742,474 (13.3 cases per 1,000 inhabitants) and 510,206 (9.0 cases per 1,000 inhabitants), respectively. There are significant differences by conditions groups, age, length of stay, severity level, and proportion of medical stays between the Weissman and Ansari methods. CONCLUSIONS: Regarding potentially avoidable hospitalizations in France in 2012, the agreement between the Weissman and Ansari approaches is poor. The method used to measure potentially avoidable hospitalizations is critical, and might influence the assessment of accessibility and performance of primary care.

The diagnostic challenge of myocardial infarction in critically ill patients: do high-sensitivity troponin measurements add more clarity or more confusion?

In ICU settings, the diagnosis and treatment of acute myocardial infarction (AMI) are challenging, partly because cardiac troponin increase occurs frequently. In the previous issue of Critical Care, Ostermann and colleagues reported that myocardial infarction (MI), screened by plasma troponin and electrocardiography changes, is common and often clinically unrecognized in the ICU. Although the clinical significance of underdiagnosed MIs remains unclear, this approach may help to target and further investigate the at-risk population for appropriate therapy.

Plasma brain natriuretic peptide and troponin levels in severe sepsis and septic shock: relationships with systolic myocardial dysfunction and intensive care unit mortality.

The aim of this study was to evaluate and compare brain natriuretic peptide (BNP) and cardiac troponin I (cTnI) levels as mortality prognosticator and predictor for myocardial dysfunction in severe sepsis and septic shock. Baseline clinical and biological variables were collected from 47 patients with severe sepsis or septic shock. Ventricular systolic function assessed by echocardiography was measured over a 5-day period. Both cTnI and BNP plasmatic levels were determined at intensive care unit (ICU) admission and during the following 15 days. At admission, cTnI and BNP levels were compared to those of 12 control critically ill nonseptic patients. The plasma levels of BNP and cTnI in patients with sepsis were elevated at admission and significantly higher than in the controls. Among patients with sepsis, BNP levels were significantly more elevated in nonsurvivors compared to survivors at admission and 1 day later. The cTnI levels were also significantly more elevated in nonsurvivors compared to survivors, but only at admission. From admission to day 5, patients with sepsis with left ventricular systolic dysfunction had higher BNP plasmatic concentrations than those without; differences were significant at days 3 and 4. In contrast, plasma cTnI levels were similar between the 2 groups. In critically ill patients, sepsis induces significant increase in BNP and cTnI levels. High BNP and cTnI plasma levels during ICU admission appear to be associated with poor outcome of sepsis. Time course of BNP levels seems helpful to discriminate between surviving and nonsurviving patients with sepsis and to detect myocardial dysfunction where troponin levels fail to do so.

Prognosis and ICU outcome of systemic vasculitis.

BACKGROUND: Systemic vasculitis may cause life threatening complications requiring admission to an intensive care unit (ICU). The aim of this study was to evaluate outcomes of systemic vasculitis patients admitted to the ICU and to identify prognosis factors. METHODS: During a ten-year period, records of 31 adult patients with systemic vasculitis admitted to ICUs (median age: 63 y.o, sex ratio M/F: 21/10, SAPS II: 40) were reviewed including clinical and biological parameters, use of mechanical ventilation, catecholamine or/and dialysis support. Mortality was assessed and data were analyzed to identify predictive factors of outcome. RESULTS: Causes of ICU admissions were active manifestation of vasculitis (n = 19), septic shock (n = 8) and miscellaneous (n = 4). Sixteen patients (52%) died in ICU. By univariate analysis, mortality was associated with higher SOFA (p = 0.006) and SAPS II (p = 0.004) scores. The need for a catecholamine support or/and a renal replacement therapy, and the occurrence of an ARDS significantly worsen the prognosis. By multivariate analysis, only SAPS II (Odd ratio: 1.16, 95% CI [1.01; 1.33]) and BVAS scores (Odd ratio: 1.16, 95% CI = [1.01; 1.34]) were predictive of mortality. CONCLUSION: The mortality rate of severe vasculitis requiring an admission to ICU was high. High levels of SAPS II and BVAS scores at admission were predictive of mortality.

Clinical review of eight patients with acute respiratory distress syndrome due to pulmonary tuberculosis.

Pulmonary tuberculosis can lead to acute respiratory distress syndrome (ARDS) even in the absence of superinfection, and this condition requires mechanical ventilation. We describe herein the characteristics and outcomes of 8 patients with this association hospitalized in a French teaching hospital between 1997 and 2006.

Implementing on-line hemodiafiltration as a renal replacement therapy for ICU acute renal failure: a single-center report of feasibility, safety and hemodynamic tolerance over a seven-year period.

BACKGROUND/AIMS: On-line hemodiafiltration (HDF) is not yet routinely used in ICUs given the potential risk of microbial contamination of dialysis fluids. We evaluated the safety and the tolerance of its use in our ICU. METHODS: A weekly measurement of bacterial growth (CFU/ml) and endotoxin level (endotoxin units/ml) was performed in dialysis fluids over a 7-year period. Intradialytic hypotensive events and pyrogenic reactions were collected during 466 on-line HDF sessions. RESULTS: A bacterial count <0.1 CFU/ml was achieved in 977/978, 288/290, and 278/280, and an endotoxin level <0.03 endotoxin units/ml in 564/576, 330/337 and 318/323 ultrapure water, dialysate, and infusate samples, respectively. Seventy-six intradialytic hypotensive events but no pyrogenic reaction occurred. CONCLUSION: The great majority of dialysis fluid samples were considered suitable with a 99% compliance rate. Use of on-line HDF, at a large scale of dialysate and infusate flows, is well tolerated and may be safely performed in critically ill.

Severe metabolic or mixed acidemia on intensive care unit admission: incidence, prognosis and administration of buffer therapy. A prospective, multiple-center study.

INTRODUCTION: In this study, we sought describe the incidence and outcomes of severe metabolic or mixed acidemia in critically ill patients as well as the use of sodium bicarbonate therapy to treat these illnesses. METHODS: We conducted a prospective, observational, multiple-center study. Consecutive patients who presented with severe acidemia, defined herein as plasma pH below 7.20, were screened. The incidence, sodium bicarbonate prescription and outcomes of either metabolic or mixed severe acidemia were analyzed. RESULTS: Among 2, 550 critically ill patients, 200 (8%) presented with severe acidemia, and 155 (6% of the total admissions) met the inclusion criteria. Almost all patients needed mechanical ventilation and vasopressors during their ICU stay, and 20% of them required renal replacement therapy within the first 24 hours of their ICU stay. Severe metabolic or mixed acidemia was associated with a mortality rate of 57% in the ICU. Delay of acidemia recovery as opposed to initial pH value was associated with increased mortality in the ICU. The type of acidemia did not influence the decision to administer sodium bicarbonate. CONCLUSIONS: The incidence of severe metabolic or mixed acidemia in critically ill patients was 6% in the present study, and it was associated with a 57% mortality rate in the ICU. In contradistinction with the initial acid-base parameters, the rapidity of acidemia recovery was an independent risk factor for mortality. Sodium bicarbonate prescription was very heterogeneous between ICUs. Further studies assessing specific treatments may be of interest in this population.

Factors influencing adherence to continuous positive airway pressure devices in individuals with spinal cord injury and sleep apnea: Results of a qualitative study.

BACKGROUND: In individuals with spinal cord injury (SCI) and sleep apnea (SA), adherence to continuous positive airway pressure (CPAP) therapy seems unsatisfactory despite technical and educational support implemented when starting treatment. OBJECTIVE: We aimed to design comprehensive model of adherence to CPAP therapy in individuals with SCI and SA. METHODS: This was a prospective qualitative study based on semi-directed interviews and using the grounded theory as an analytic method. The theoretical framework was the social cognitive theory of Bandura. Participants were recruited from an SCI referral centre. Individuals with SCI using or having used a CPAP device for SA were included. Data were collected by semi-directed interviews on the experience of individuals with SCI regarding SA and being fitted with a CPAP device and were coded and organized into categories of experience and category relationships. RESULTS: Among the 17 individuals included; 9 had tetraplegia; the median age was 62 (Q1-Q3 47-66) years and median time since injury was 16 (Q1-Q3 1.75-21) years. Four categories of data were identified: 1) from symptoms to validation of SA diagnosis, 2) CPAP device fitting process, 3) representations of SA, and 4) level of adherence to the treatment. In addition to the factors already observed in the general population, the proposed model identified specific adherence factors in individuals with SCI, such as physical and relational dependence on a third party, increased daily care burden and increased presence of medical devices in the daily environment. CONCLUSION: SA and its management present certain specificities in individuals with SCI that the physician must take into account to optimize therapeutic proposals, follow-up modalities and device adherence.

Quality assessment in intensive care units: proposal for a scoring system in terms of structure and process.

OBJECTIVE: We present a score for assessing the quality of ICU care in terms of structure and process, based on bibliographic review, expert consultations, field test, analysis, and final consensus, and analyze its initial application in the field. DESIGN AND SETTING: This feasibility and observational study was conducted within the framework of a French regional clinical research project (NosoQual); 40 ICUs were visited and assessed between November 2002 and March 2003 according to standardized procedures. MEASUREMENTS AND RESULTS: The grid consisted of 95 variables. The overall score derived from seven independent quality dimensions: human resources, architecture, safety and environment, management of documentation, patient care management, risk management of infections and evaluation, and surveillance. The average level of achievement of the scores varied from 48% to 63% of theoretical maxima. Variability in the individual dimensional subscores was greater than that of the overall score (CV=15). CONCLUSIONS: Evaluation this scoring system encounters the limitation of the absence of a "gold standard." However, this is counterbalanced by the rigorous design methodology, the characteristic strengths of the quality dimensions. The survey also highlights also feasibility and the potential interest for specific tools for the assessment of ICUs.

Urinary Biomarkers IGFBP7 and TIMP-2 for the Diagnostic Assessment of Transient and Persistent Acute Kidney Injury in Critically Ill Patients.

OBJECTIVE: The capability of urinary TIMP-2 (tissue inhibitor of metalloproteinase) and IGFBP7 (insulin-like growth factor binding protein)-NephroCheck Test (NC) = ([TIMP-2] x [IGFBP7]) / 1000)-to predict renal recovery from acute kidney injury (AKI) has been poorly studied. The aim of this study was to assess the performance of measurements of ([TIMP-2] x [IGFBP7]) / 1000) over 24 hours to differentiate transient from persistent AKI. METHODS: Of 460 consecutive adult patients admitted to the ICU, 101 were prospectively studied: 56 men, 62 (52-71) years old. A fresh urine sample was collected at H0, H4, H12 and H24 to determine ([TIMP-2] x [IGFBP7]) / 1000) levels. Areas under the curves of Delta NC H4-Ho and H12-H4 and serum creatinine (sCr) for detection of AKI recovery were compared. RESULTS: Forty-one (40.6%) patient were diagnosed with AKI: 27 transient and 14 persistent AKI. At admission (H0), AKI patients had a significantly higher NC score than patients without AKI (0.43 [0.07-2.06] vs 0.15 [0.07-0.35], p = 0.027). In AKI groups, transient AKI have a higher NC, at H0 and H4, than persistent AKI (0.87 [0.09-2.82] vs 0.13 [0.05-0.66] p = 0.035 and 0.13 [0.07-0.61] vs 0.05 [0.02-0.13] p = 0.013). Thereafter, NC level decreased in both AKI groups with a Delta NC score H4-H0 and H12-H4 significantly more important in transient AKI. Roc curves showed however that delta NC scores did not discriminate between transient and persistent AKI. CONCLUSION: In our population, absolute urinary levels of NC score were higher at early hours after ICU admission (H0 and H4) in transient AKI as compared to persistent AKI patients. NC variations (Delta NC scores) over the first 12 hours may indicate the AKI's evolving nature with a more significant decrease in case of transient AKI but were not able to differentiate transient from persistent AKI.

Daily urinary creatinine predicts the weaning of renal replacement therapy in ICU acute kidney injury patients.

BACKGROUND: In acute kidney injury (AKI), useless continuation of renal replacement therapy (RRT) may delay renal recovery and impair patient's outcome. In this study, we aimed to identify predictive parameters that may help to a successful RRT weaning for AKI patients. METHODS: We studied 54 surviving AKI patients in which a weaning of RRT was attempted. On the day of weaning (D0) and the following 2 days (D1 and D2), SAPS II and SOFA scores, 24-h diuresis, 24-h urinary creatinine and urea (UCr and UUr), creatinine and urea generation rates (CrGR and UrGR) and clearances (CrCl and UrCl) were collected. Patients who remained free of RRT 15 days after its discontinuation were considered as successfully weaned. RESULTS: Twenty-six RRT weaning attempts succeeded (S+) and 28 failed (S-). Age, previous renal function, SAPS II and SOFA scores were comparable between groups. At D0, 24-h diuresis was 2300 versus 1950 ml in S+ and S-, respectively, p = 0.05. At D0, D1 and D2, 24-h UUr and UCr levels, UrCl and CrCl, and UUr/UrGR and UCr/CrGR ratios were significantly higher in S+ group. By multivariate analysis, D1 24-h UCr was the most powerful parameter that was associated with RRT weaning success with an area under the ROC curve of 0.86 [0.75-0.97] and an odds ratio of 2.01 [1.27-3.18], p = 0.003. CONCLUSIONS: In ICU AKI, 24-h UCr appeared as an efficient and independent marker of a successful weaning of RRT. A 24-h UCr ≥5.2 mmol was associated with a successful weaning in 84 % of patients.

Diagnostic and prognostic value of soluble CD14 subtype (Presepsin) for sepsis and community-acquired pneumonia in ICU patients.

BACKGROUND: The soluble CD14 subtype, Presepsin, appears to be an accurate sepsis diagnostic marker, but data from intensive care units (ICUs) are scarce. This study was conducted to evaluate the diagnostic and prognostic value of Presepsin in ICU patients with severe sepsis (SS), septic shock (SSh) and severe community-acquired pneumonia (sCAP). METHODS: Presepsin and procalcitonin (PCT) levels were determined for patients at admission to ICU. Four groups have been differentiated: (1) absence or (2) presence of systemic inflammatory response syndrome, (3) SS or (4) SSh; and 2 groups, among the patients admitted for acute respiratory failure: absence or presence of sCAP. Biomarkers were tested for diagnosis of SS, SSh and sCAP and for prediction of ICU mortality. RESULTS: One hundred and forty-four patients were included: 44 SS and 56 SSh. Plasma levels of Presepsin and PCT were significantly higher in septic than in non-septic patients and in SSh as compared to others. The sepsis diagnostic accuracy of Presepsin was not superior to that of PCT (AUC: 0.75 vs 0.80). In the 72/144 patients admitted for acute respiratory failure, the capability of Presepsin to diagnose sCAP was significantly better than PCT. Presepsin levels were also predictive of ICU mortality in sepsis and in sCAP patients. CONCLUSION: Plasma levels of Presepsin were useful for the diagnosis of SS, SSh and sCAP and may predict ICU mortality in these patients.

Systems medicine approaches for the definition of complex phenotypes in chronic diseases and ageing. From concept to implementation and policies.

Chronic diseases are diseases of long duration and slow progression. Major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, diabetes, rheumatologic diseases and mental health) represent the predominant health problem of the Century. The prevention and control of NCDs are the priority of the World Health Organization 2008 Action Plan, the United Nations 2010 Resolution and the European Union 2010 Council. The novel trend for the management of NCDs is evolving towards integrative, holistic approaches. NCDs are intertwined with ageing. The European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has prioritised NCDs. To tackle them in their totality in order to reduce their burden and societal impact, it is proposed that NCDs should be considered as a single expression of disease with different risk factors and entities. An innovative integrated health system built around systems medicine and strategic partnerships is proposed to combat NCDs. It includes (i) understanding the social, economic, environmental, genetic determinants, as well as the molecular and cellular mechanisms underlying NCDs; (ii) primary care and practice-based interprofessional collaboration; (iii) carefully phenotyped patients; (iv) development of unbiased and accurate biomarkers for comorbidities, severity and follow up of patients; (v) socio-economic science; (vi) development of guidelines; (vii) training; and (viii) policy decisions. The results could be applicable to all countries and adapted to local needs, economy and health systems. This paper reviews the complexity of NCDs intertwined with ageing. It gives an overview of the problem and proposes two practical examples of systems medicine (MeDALL) applied to allergy and to NCD co-morbidities (MACVIA-LR, Reference Site of the European Innovation Partnership on Active and Healthy Ageing).

Feasibility of hypothermia beyond 3 weeks in severe ischemic stroke: an open pilot study using γ-hydroxybutyrate.

PURPOSE: Hypothermia is a promising neuroprotective therapy. We studied the feasibility and safety of very prolonged moderate hypothermia for severe acute ischemic stroke. METHODS: Moderate hypothermia was induced within 24h after a severe ischemic stroke involving the middle cerebral artery. Hypothermia, with cooling blankets, reduced body-core temperature to 32-33°C, and was prolonged for up to 22 days until cerebral edema had significantly decreased (assessed by serial cerebral computed tomography) before slow rewarming (<1.5°C/day). Patients were mechanically ventilated and sedated with gamma-hydroxybutyrate (GHB), a naturally occurring metabolite of gamma-aminobutyric acid (GABA), which acts on the GABA(B) receptors. Outcomes and side effects at 12 months were recorded. RESULTS: Nineteen patients (mean age: 52.6 years, mean National Institute of Health Stroke Scale (NIHSS) score 21) were enrolled. Cooling was achieved in all patients. The mean time to reach target temperature was 11.4 ± 8.6h and the mean duration of rewarming was 4.0 ± 1.1 days. For the 10 survivors (53%), the mean duration of hypothermia and rewarming was 22.6 ± 4.9 days. Five patients underwent a hemicraniectomy. All patients presented with hypotension, bradycardia, and hematological side effects. Eight patients had pneumonia (42%). At 12 months, the mean NIHSS score was 8.3 ± 2.7, the Barthel Index was 67 ± 18, and the modified Rankin scale was 3.2 ± 0.9. CONCLUSIONS: This study shows the feasibility of very prolonged hypothermia beyond 3 weeks using GHB sedation in severe hemispheric infarcts.

Short- and long-term outcomes of HIV-infected patients admitted to the intensive care unit: impact of antiretroviral therapy and immunovirological status.

BACKGROUND: The purpose of this study was to assess the short- and long-term outcomes of HIV-infected patients admitted to intensive care units (ICU) according to immunovirological status at admission and highly active antiretroviral therapy (HAART) use in ICU. METHODS: Retrospective study of 98 HIV-infected patients hospitalized between 1997 and 2008 in two medical ICU in Montpellier, France. The primary outcome was mortality in ICU. The secondary end point was probability of survival in the year following ICU admission. RESULTS: Eighty-two (83.6%) admissions in ICU were related to HIV infection and 45% of patients had received HAART before admission. Sixty-two patients (63.3%) were discharged from ICU, and 34 (34.7%) were alive at 1 year. Plasma HIV RNA viral load (VL) and CD4+ cell count separately were not associated with outcome. Independent predictors of ICU mortality were the use of vasopressive agents (odds ratio (OR), 3.779; 95% confidence interval (CI), 1.11-12.861; p = 0.0334) and SAPS II score (OR, 1.04; 95% CI, 1.003-1.077; p = 0.0319), whereas introducing or continuing HAART in ICU was protective (OR, 0.278; 95% CI, 0.082-0.939; p = 0.0393). Factors independently associated with 1-year mortality were immunovirological status with high VL (>3 log10/ml) and low CD4 (<200/mm3; hazard ratio (HR), 5.19; 95% CI, 1.328-20.279; p = 0.0179) or low VL (<3 log10/ml) and low CD4 (HR, 4.714; 95% CI, 1.178-18.867; p = 0.0284) vs. high CD4 and low VL, coinfection with C hepatitis virus (HR, 3.268; 95% CI, 1.29-8.278; p = 0.0125), the use of vasopressive agents (HR, 3.68; 95% CI, 1.394-9.716; p = 0.0085), and SAPS II score (HR, 1.09; 95% CI, 1.057-1.124; p <0.0001). Introducing HAART in a patient with no HAART at admission was associated with a better long-term outcome (HR, 0.166; 95% CI, 0.043-0.642; p = 0.0093). CONCLUSIONS: In a population of HIV-infected patients admitted to ICU, short- and long-term outcomes are related to acute illness severity and immunovirological status at admission. Complementary studies are necessary to identify HIV-infected patients who benefit from HAART use in ICU according to immunovirological status and the reasons of ICU admission.

Motor and respiratory heterogeneity in Duchenne patients: implication for clinical trials.

AIMS: Our objective was to clarify the clinical heterogeneity in Duchenne muscular dystrophy (DMD). METHODS: The French dystrophinopathy database provided clinical, histochemical and molecular data of 278 DMD patients (mean longitudinal follow-up: 14.2 years). Diagnosis was based on mutation identification in the DMD gene. Three groups were defined according to the age at ambulation loss: before 8 years (group A); between 8 and 11 years (group B); between 11 and 16 years (group C). RESULTS: Motor and respiratory declines were statistically different between the three groups, as opposed to heart involvement. When acquired, running ability was lost at the mean age of 5.41 (group A), 7.11 (group B), 9.19 (group C) years; climbing stairs ability at 6.24 (group A), 7.99 (group B), 10,42 (group C) years, and ambulation at 7.10 (group A), 9.25 (group B), 12.01 (group C) years. Pulmonary growth stopped at 10.26 (group A), 12.45 (group B), 14.58 (group C) years. Then, forced vital capacity decreased at the rate of 8.83 (group A), 7.52 (group B), 6.03 (group C) percent per year. Phenotypic variability did not rely on specific mutational spectrum. CONCLUSION: Beside the most common form of DMD (group B), we provide detailed description on two extreme clinical subgroups: a severe one (group A) characterized by early severe motor and respiratory decline and a milder subgroup (group C). Compared to group B or C, four to six times fewer patients from group A are needed to detect the same decrease in disease progression in a clinical trial.